Author: "Corneau A" / Topic: medicine - Searchworks@Jio Institute Digital Library Search Results

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127 results on '"Corneau A"'

1. Comprehensive analysis of early T cell responses to acute Zika Virus infection during the first epidemic in Bahia, Brazil.

Author: Assia Samri, Antonio Carlos Bandeira, Luana Leandro Gois, Carlos Gustavo Regis Silva, Alice Rousseau, Aurelien Corneau, Nadine Tarantino, Christopher Maucourant, Gabriel Andrade Nonato Queiroz, Vincent Vieillard, Hans Yssel, Gubio Soares Campos, Silvia Sardi, Brigitte Autran, and Maria Fernanda Rios Grassi
Subjects: Medicine, Science
Abstract: BackgroundIn most cases, Zika virus (ZIKV) causes a self-limited acute illness in adults, characterized by mild clinical symptoms that resolve within a few days. Immune responses, both innate and adaptive, play a central role in controlling and eliminating virus-infected cells during the early stages of infection.AimTo test the hypothesis that circulating T cells exhibit phenotypic and functional activation characteristics during the viremic phase of ZIKV infection.MethodsA comprehensive analysis using mass cytometry was performed on peripheral blood mononuclear cells obtained from patients with acute ZIKV infection (as confirmed by RT-PCR) and compared with that from healthy donors (HD). The frequency of IFN-γ-producing T cells in response to peptide pools covering immunogenic regions of structural and nonstructural ZIKV proteins was quantified using an ELISpot assay.ResultsCirculating CD4+ and CD8+ T lymphocytes from ZIKV-infected patients expressed higher levels of IFN-γ and pSTAT-5, as well as cell surface markers associated with proliferation (Ki-67), activation ((HLA-DR, CD38) or exhaustion (PD1 and CTLA-4), compared to those from HD. Activation of CD4+ and CD8+ memory T cell subsets, including Transitional Memory T Cells (TTM), Effector Memory T cells (TEM), and Effector Memory T cells Re-expressing CD45RA (TEMRA), was prominent among CD4+ T cell subset of ZIKV-infected patients and was associated with increased levels of IFN-γ, pSTAT-5, Ki-67, CTLA-4, and PD1, as compared to HD. Additionally, approximately 30% of ZIKV-infected patients exhibited a T cell response primarily directed against the ZIKV NS5 protein.ConclusionCirculating T lymphocytes spontaneously produce IFN-γ and express elevated levels of pSTAT-5 during the early phase of ZIKV infection whereas recognition of ZIKV antigen results in the generation of virus-specific IFN-γ-producing T cells.
Published: 2024
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2. CD8+PD-L1+CXCR3+ polyfunctional T cell abundances are associated with survival in critical SARS-CoV-2–infected patients

Author: Lucille Adam, Pierre Rosenbaum, Paul Quentric, Christophe Parizot, Olivia Bonduelle, Noëlline Guillou, Aurélien Corneau, Karim Dorgham, Makoto Miyara, Charles-Edouard Luyt, Amélie Guihot, Guy Gorochov, Christophe Combadière, and Behazine Combadière
Subjects: Immunology, Medicine
Abstract: The importance of the adaptive T cell response in the control and resolution of viral infection has been well established. However, the nature of T cell–mediated viral control mechanisms in life-threatening stages of COVID-19 has yet to be determined. The aim of the present study was to determine the function and phenotype of T cell populations associated with survival or death of patients with COVID-19 in intensive care as a result of phenotypic and functional profiling by mass cytometry. Increased frequencies of circulating, polyfunctional CD4+CXCR5+HLA-DR+ stem cell memory T cells (Tscms) and decreased proportions of granzyme B–expressing and perforin-expressing effector memory T cells were detected in recovered and deceased patients, respectively. The higher abundance of polyfunctional PD-L1+CXCR3+CD8+ effector T cells (Teffs), CXCR5+HLA-DR+ Tscms, and anti-nucleocapsid (anti-NC) cytokine-producing T cells permitted us to differentiate between recovered and deceased patients. The results from a principal component analysis show an imbalance in the T cell compartment that allowed for the separation of recovered and deceased patients. The paucity of circulating PD-L1+CXCR3+CD8+ Teffs and NC-specific CD8+ T cells accurately forecasts fatal disease outcome. This study provides insight into the nature of the T cell populations involved in the control of COVID-19 and therefore might impact T cell–based vaccine designs for this infectious disease.
Published: 2021
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3. UM171 induces a homeostatic inflammatory-detoxification response supporting human HSC self-renewal.

Author: Jalila Chagraoui, Bernhard Lehnertz, Simon Girard, Jean Francois Spinella, Iman Fares, Elisa Tomellini, Nadine Mayotte, Sophie Corneau, Tara MacRae, Laura Simon, and Guy Sauvageau
Subjects: Medicine, Science
Abstract: Elucidation of the molecular cues required to balance adult stem cell self-renewal and differentiation is critical for advancing cellular therapies. Herein, we report that the hematopoietic stem cell (HSC) self-renewal agonist UM171 triggers a balanced pro- and anti-inflammatory/detoxification network that relies on NFKB activation and protein C receptor-dependent ROS detoxification, respectively. We demonstrate that within this network, EPCR serves as a critical protective component as its deletion hypersensitizes primitive hematopoietic cells to pro-inflammatory signals and ROS accumulation resulting in compromised stem cell function. Conversely, abrogation of the pro-inflammatory activity of UM171 through treatment with dexamethasone, cAMP elevating agents or NFkB inhibitors abolishes EPCR upregulation and HSC expansion. Together, these results show that UM171 stimulates ex vivo HSC expansion by establishing a critical balance between key pro- and anti-inflammatory mediators of self-renewal.
Published: 2019
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4. HLFexpression defines the human hematopoietic stem cell state

Author: Tara MacRae, Deanne Gracias, Nadine Mayotte, Sophie Corneau, Elisa Tomellini, Guy Sauvageau, Jalila Chagraoui, Isabel Boivin, Bernhard Lehnertz, and Aurelie Durand
Subjects: education.field_of_study, Immunology, Population, Gene Expression, Hematopoietic stem cell, Cell Biology, Hematology, Biology, Hematopoietic Stem Cells, Biochemistry, Hepatic Leukemia Factor, Hematopoiesis, Cell biology, Blood cell, Transplantation, Haematopoiesis, Basic-Leucine Zipper Transcription Factors, medicine.anatomical_structure, medicine, Humans, Bone marrow, Single-Cell Analysis, Stem cell, Transcriptome, education
Abstract: Hematopoietic stem cells (HSCs) sustain blood cell homeostasis throughout life and can regenerate all blood lineages after transplantation. Despite this clear functional definition, highly enriched isolation of human HSCs can currently only be achieved through combinatorial assessment of multiple surface antigens. Although several transgenic HSC reporter mouse strains have been described, no analogous approach to prospectively isolate human HSCs has been reported. To identify genes with the most selective expression in human HSCs, we profiled population and single-cell transcriptomes of unexpanded and ex vivo cultured cord blood–derived hematopoietic stem and progenitor cells as well as peripheral blood, adult bone marrow, and fetal liver. On the basis of these analyses, we propose the master transcription factor HLF (hepatic leukemia factor) as one of the most specific HSC marker genes. To directly track its expression in human hematopoietic cells, we developed a genomic HLF reporter strategy, capable of selectively labeling the most immature blood cells on the basis of a single engineered parameter. Most importantly, HLF-expressing cells comprise all stem cell activity in culture and in vivo during serial transplantation. Taken together, these results experimentally establish HLF as a defining gene of the human HSC state and outline a new approach to continuously mark these cells with high fidelity.
Published: 2021

5. Analysis of cell surface and intranuclear markers on non-stimulated human PBMC using mass cytometry.

Author: Gaëlle Dzangué-Tchoupou, Aurélien Corneau, Catherine Blanc, Olivier Benveniste, and Yves Allenbach
Subjects: Medicine, Science
Abstract: Mass cytometry is a powerful tool that allows simultaneous analysis of more than 37 markers at the single cell level. Mass cytometry is of particular interest in the identification of a wide variety of cell phenotypes in autoimmune diseases. Moreover, cells can be labelled with palladium isotopes and pooled before staining (barcoding). Nevertheless, immunologists often face an important problem concerning the choice of markers to be included in a panel. This problem arises due to the incompatibility of different buffers used for the fixation and permeabilization of cells with various cell surface epitopes. In this study, we used a panel of 27 markers (19 surface markers and 8 intranuclear markers) to demonstrate disparities in the detection of cell surface antigens when comparing different buffers to stain unstimulated peripheral blood mononuclear cells. These disparities range from mild differences to very important differences in population frequencies depending on the buffers. Finally, we demonstrate the harmful effects of permeabilization prior to barcoding on the detection of some cell surface antigens. Here, we optimize a protocol that is suitable to use when targeting a large panel including both cell surface and intranuclear markers on unstimulated human peripheral blood mononuclear cells.
Published: 2018
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6. Survival and Inactivation by Advanced Oxidative Process of Foodborne Viruses in Model Low-Moisture Foods

Author: Nathalie Corneau, Angela Chen, Sabah Bidawid, Neda Nasheri, and Jennifer Harlow
Subjects: 0301 basic medicine, Advanced oxidative process, Epidemiology, Health, Toxicology and Mutagenesis, viruses, 030106 microbiology, ved/biology.organism_classification_rank.species, Norovirus surrogates, Low-moisture foods, Food Contamination, medicine.disease_cause, Bead-based assay, Foodborne Diseases, 03 medical and health sciences, Mice, 0302 clinical medicine, Ozone, Virology, Food Preservation, medicine, Animals, 030212 general & internal medicine, Chocolate, Infectivity, Virus quantification, Feline calicivirus, Original Paper, biology, ved/biology, Infectious dose, Norovirus, Outbreak, Water, Hydrogen Peroxide, biology.organism_classification, Food Storage, Pistacia, Food Preservatives, Virus Inactivation, Vaporized hydrogen peroxide, Hepatitis A virus, Edible Grain, Oxidation-Reduction, Food Science, Murine norovirus, Calicivirus, Feline
Abstract: Enteric viruses, such as human norovirus (NoV) and hepatitis A virus (HAV), are the major causes of foodborne illnesses worldwide. These viruses have low infectious dose, and may remain infectious for weeks in the environment and food. Limited information is available regarding viral survival and transmission in low-moisture foods (LMF). LMFs are generally considered as ready-to-eat products, which undergo no or minimal pathogen reduction steps. However, numerous foodborne viral outbreaks associated with LMFs have been reported in recent years. The objective of this study was to examine the survival of foodborne viruses in LMFs during 4-week storage at ambient temperature and to evaluate the efficacy of advanced oxidative process (AOP) treatment in the inactivation of these viruses. For this purpose, select LMFs such as pistachios, chocolate, and cereal were inoculated with HAV and the norovirus surrogates, murine norovirus (MNV) and feline calicivirus (FCV), then viral survival on these food matrices was measured over a four-week incubation at ambient temperature, by both plaque assay and droplet-digital RT-PCR (ddRT-PCR) using the modified ISO-15216 method as well as the magnetic bead assay for viral recovery. We observed an approximately 0.5 log reduction in viral genome copies, and 1 log reduction in viral infectivity for all three tested viruses following storage of select inoculated LMFs for 4 weeks. Therefore, the present study shows that the examined foodborne viruses can persist for a long time in LMFs. Next, we examined the inactivation efficacy of AOP treatment, which combines UV-C, ozone, and hydrogen peroxide vapor, and observed that while approximately 100% (4 log) inactivation can be achieved for FCV, and MNV in chocolate, the inactivation efficiency diminishes to approximately 90% (1 log) in pistachios and 70% (
Published: 2021

7. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19

Author: Zhang Q., Liu Z., Moncada-Velez M., Chen J., Ogishi M., Bigio B., Yang R., Arias A. A., Zhou Q., Han J. E., Ugurbil A. C., Zhang P., Rapaport F., Li J., Spaan A. N., Boisson B., Boisson-Dupuis S., Bustamante J., Puel A., Ciancanelli M. J., Zhang S. -Y., Beziat V., Jouanguy E., Abel L., Cobat A., Casanova J. -L., Bastard P., Korol C., Rosain J., Philippot Q., Chbihi M., Lorenzo L., Bizien L., Neehus A. -L., Kerner G., Seeleuthner Y., Manry J., Le Voyer T., Le Pen J., Schneider W. M., Razooky B. S., Hoffmann H. -H., Michailidis E., Rice C. M., Sabli I. K. D., Hodeib S., Sancho-Shimizu V., Bilguvar K., Ye J., Maniatis T., Bolze A., Zhang Y., Notarangelo L. D., Su H. C., Onodi F., Korniotis S., Karpf L., Soumelis V., Bonnet-Madin L., Amara A., Dorgham K., Gorochov G., Smith N., Duffy D., Moens L., Meyts I., Meade P., Garcia-Sastre A., Krammer F., Corneau A., Masson C., Schmitt Y., Schluter A., Pujol A., Khan T., Marr N., Fellay J., Roussel L., Vinh D. C., Shahrooei M., Alosaimi M. F., Alsohime F., Hasanato R., Mansouri D., Al-Saud H., Almourfi F., Al-Mulla F., Al-Muhsen S. Z., Al Turki S., van de Beek D., Biondi A., Bettini L. R., D'Angio M., Bonfanti P., Imberti L., Sottini A., Paghera S., Quiros-Roldan E., Rossi C., Oler A. J., Tompkins M. F., Alba C., Dalgard C. L., Vandernoot I., Smits G., Goffard J. -C., Migeotte I., Haerynck F., Soler-Palacin P., Martin-Nalda A., Colobran R., Morange P. -E., Keles S., Colkesen F., Ozcelik T., Yasar K. K., Senoglu S., Karabela S. N., Rodriguez-Gallego C., Novelli G., Hraiech S., Tandjaoui-Lambiotte Y., Duval X., Laouenan C., Snow A. L., Milner J. D., Mogensen T. H., Nussenzweig M., Lifton R. P., Foti G., Bellani G., Citerio G., Contro E., Pesci A., Valsecchi M. G., Cazzaniga M., Abad J., Blanco I., Rodrigo C., Aguilera-Albesa S., Akcan O. M., Darazam I. A., Aldave J. C., Ramos M. A., Nadji S. A., Alkan G., Allardet-Servent J., Allende L. M., Alsina L., Alyanakian M. -A., Amador-Borrero B., Mouly S., Sene D., Amoura Z., Mathian A., Antoli A., Blanch G. R., Riera J. S., Moreno X. S., Arslan S., Assant S., Auguet T., Azot A., Bajolle F., Levy R., Oualha M., Baldolli A., Ballester M., Feldman H. B., Barrou B., Beurton A., Bilbao A., Blanchard-Rohner G., Blandinieres A., Rivet N., Blazquez-Gamero D., Bloomfield M., Bolivar-Prados M., Clave P., Borie R., Bosteels C., Lambrecht B. N., van Braeckel E., Bousfiha A. A., Bouvattier C., Vincent A., Boyarchuk O., Bueno M. R. P., Castro M. V., Matos L. R. B., Zatz M., Agra J. J. C., Calimli S., Capra R., Carrabba M., Fabio G., Casasnovas C., Velez-Santamaria V., Caseris M., Falck A., Poncelet G., Castelle M., Castelli F., de Vera M. C., Catherinot E., Chalumeau M., Toubiana J., Charbit B., Li Z., Pellegrini S., Cheng M. P., Clotet B., Codina A., Comarmond C., Dalmau D., Darley D. R., Dauby N., Dauger S., Le Bourgeois F., Levy M., de Pontual L., Dehban A., Delplancq G., Demoule A., Diehl J. -L., Dobbelaere S., Durand S., Mircher C., Rebillat A. -S., Vilaire M. E., Eldars W., Elgamal M., Elnagdy M. H., Emiroglu M., Erdeniz E. H., Aytekin S. E., Euvrard R., Evcen R., Faivre L., Fartoukh M., Faure M., Arquero M. F., Flores C., Francois B., Fumado V., Fusco F., Ursini M. V., Solis B. G., de Diego R. P., van Den Rym A. M., Gaussem P., Gil-Herrera J., Gilardin L., Alarcon M. G., Girona-Alarcon M., Gok F., Yosunkaya A., Gonzalez-Montelongo R., Inigo-Campos A., Lorenzo-Salazar J. M., Munoz-Barrera A., Guerder A., Gul Y., Guner S. N., Gut M., Hadjadj J., Halwani R., Hammarstrom L., Hatipoglu N., Hernandez-Brito E., Heijmans C., Holanda-Pena M. S., Horcajada J. P., Hoste L., Hoste E., Humbert L., Mordacq C., Thumerelle C., Vuotto F., Iglesias A. D., Jamme M., Arranz M. J., Jordan I., Jorens P., Kanat F., Kapakli H., Kara I., Karbuz A., Demirkol Y. K., Klocperk A., Krol Z. J., Kuentz P., Kwan Y. W. M., Lagier J. -C., Lau Y. -L., Leung D., Leo Y. -S., Young B. E., Lopez R. L., Levin M., Linglart A., Loeys B., Louapre C., Lubetzki C., Luyt C. -E., Lye D. C., Marjani M., Pereira J. M., Martin A., Pueyo D. M., Martinez-Picado J., Marzana I., Matthews G. V., Mayaux J., Parizot C., Quentric P., Mege J. -L., Raoult D., Melki I., Meritet J. -F., Metin O., Mezidi M., Taccone F., Millereux M., Mirault T., Mirsaeidi M., Melian A. M., Martinez A. M., Morange P., Morelle G., Naesens L., Nafati C., Neves J. F., Ng L. F. P., Medina Y. N., Cuadros E. N., Gonzalo Ocejo-Vinyals J., Orbak Z., Pan-Hammarstrom Q., Pascreau T., Paz-Artal E., Philippe A., Planas-Serra L., Ploin D., Viel S., Poissy J., Pouletty M., Reisli I., Ricart P., Richard J. -C., Riviere J. G., Rodriguez-Palmero A., Romero C. S., Rothenbuhler A., Rozenberg F., del Prado M. Y. R., Sanchez O., Sanchez-Ramon S., Schmidt M., Schweitzer C. E., Scolari F., Sediva A., Seijo L. M., Seppanen M. R. J., Ilovich A. S., Slabbynck H., Smadja D. M., Sobh A., Sole-Violan J., Soler C., Stepanovskiy Y., Stoclin A., Taupin J. -L., Tavernier S. J., Terrier B., Tomasoni G., Alvarez J. T., Trouillet-Assant S., Troya J., Tucci A., Uzunhan Y., Vabres P., Valencia-Ramos J., van de Velde S., van Praet J., Vatansev H., Vilain C., Voiriot G., Yucel F., Zannad F., Belot A., Bole-Feysot C., Lyonnet S., Nitschke P., Pouliet A., Tores F., Zarhrate M., Andrejak C., Angoulvant F., Bachelet D., Bhavsar K., Bouadma L., Chair A., Couffignal C., Silveira C. D., Debray M. -P., Eloy P., Esposito-Farese M., Ettalhaoui N., Gault N., Ghosn J., Gorenne I., Hoffmann I., Kafif O., Kali S., Khalil A., Laribi S., Le M., Le Hingrat Q., Lescure F. -X., Lucet J. C., Mentre F., Mullaert J., Peiffer-Smadja N., Peytavin G., Roy C., Schneider M., Mohammed N. S., Tagherset L., Tardivon C., Tellier M. -C., Timsit J. -F., Trioux T., Tubiana S., Basmaci R., Behillil S., Beluze M., Benkerrou D., Dorival C., Meziane A., Teoule F., Bompart F., Bouscambert M., Gaymard A., Lina B., Rosa-Calatrava M., Terrier O., Caralp M., Cervantes-Gonzalez M., D'Ortenzio E., Puechal O., Semaille C., Coelho A., Diouf A., Hoctin A., Mambert M., Couffin-Cadiergues S., Deplanque D., Descamps D., Visseaux B., Desvallees M., Khan C., Diallo A., Mercier N., Paul C., Petrov-Sanchez V., Dubos F., Enouf V. V. E., Mouquet H., Esperou H., Jaafoura S., Papadopoulos A., Etienne M., Gigante T., Rossignol B., Guedj J., Le Nagard H., Lingas G., Neant N., Kaguelidou F., Levy Y., Wiedemann A., Levy-Marchal C., Malvy D., Noret M., Pages J., Picone O., Rossignol P., Tual C., Veislinger A., van der Werf S., Vanel N., Yazdanpanah Y., Alavoine L., Costa Y., Ecobichon J. -L., Frezouls W., Ilic-Habensus E., Leclercq A., Lehacaut J., Letrou S., Mandic M., Nouroudine M., Quintin C., Rexach J., Vignali V., Amat K. K. A., Enouf V., Bielicki J., Bruijning P., Burdet C., Caumes E., Charpentier C., Damond F., Coignard B., Delmas C., Roufai L., Dechanet A., Houhou N., Kikoine J., Manchon P., Piquard V., Postolache A., Terzian Z., Lebeaux D., Lucet J. -C., Meghadecha M., Motiejunaite J., Thy M., van Agtmael M., Bomers M., Chouchane O., Geerlings S., Goorhuis B., Grobusch M. P., Harris V., Hermans S. M., Hovius J. W., Nellen J., Peters E., van der Poll T., Prins J. M., Reijnders T., Schinkel M., Sigaloff K., Stijnis C. S., van der Valk M., van Vugt M., Joost Wiersinga W., Algera A. G., van Baarle F., Bos L., Botta M., de Bruin S., Bulle E., Elbers P., Fleuren L., Girbes A., Hagens L., Heunks L., Horn J., van Mourik N., Paulus F., Raasveld J., Schultz M. J., Smit M., Stilma W., Thoral P., Tsonas A., de Vries H., Bax D., Cloherty A., Beudel M., Brouwer M. C., Koning R., Bogaard H. J., de Brabander J., de Bree G., Bugiani M., Geerts B., Hollmann M. W., Preckel B., Veelo D., Geijtenbeek T., Hafkamp F., Hamann J., Hemke R., de Jong M. D., Schuurman A., Teunissen C., Vlaar A. P. J., Wouters D., Zwinderman A. H., Aiuti A., Muhsen S. A., Anderson M. S., Bogunovic D., Itan Y., Cirulli E., Barrett K. S., Washington N., Bondarenko A., Brodin P., Bryceson Y., Bustamante C. D., Butte M., Casari G., Chakravorty S., Christodoulou J., Le Mestre S., Condino-Neto A., Cooper M. A., David A., DeRisi J. L., Desai M., Drolet B. A., Espinosa S., Franco J. L., Gregersen P. K., Hagin D., Heath J., Henrickson S. E., Hsieh E., Imai K., Karamitros T., Kisand K., Ku C. -L., Ling Y., Lucas C. L., Marodi L., Milner J., Mironska K., Mogensen T., Morio T., Novelli A., O'Farrelly C., Okada S., Planas A. M., Prando C., Quintana-Murci L., Renia L., Renieri A., Sankaran V., Snow A., Tangye S., Turvey S., Uddin F., Uddin M. J., Vazquez S. E., von Bernuth H., Zawadzki P., Jing H., Tung W., Meguro K., Shaw E., Shafer S., Zheng L., Zhang Z., Kubo S., Chauvin S. D., Lenardo M., Luthers C. R., Bauman B. M., Lack J., Karlins E., Hupalo D. M., Rosenberger J., Sukumar G., Wilkerson M. D., Zhang X., Rockefeller University [New York], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (UMR_S_944)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), R01AI088364, National Institutes of Health, Howard Hughes Medical Institute, UL1 TR001866, NIH Clinical and Translational Science Award, fast grant, Emergent Ventures, St. Giles Foundation, National Center for Advancing Translational Sciences, Rockefeller University, ANR-10-IAHU-01, Agence Nationale de la Recherche, UM1HG006504 and U24HG008956, National Human Genome Research Institute, ANR-10-LABX-62-IBEID, the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence, EQU201903007798, the French Foundation for Medical Research, Özçelik, Tayfun, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Modeling & analysis for medical imaging and Diagnosis (MYRIAD), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Virologie (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-17-CE15-0003,DENDRISEPSIS,Analyse systémique des cellules présentatrices d'antigène dans le sepsis humain(2017), ANR-20-COVI-0025,iCovid,Immunopathologie du COVID-19 à l'Assistance Publique Hôpitaux de Paris(2020), Zhang, Qian, Bastard, Paul, Le Pen, Jeremie, Moncada-Velez, Marcela, Ogishi, Masato, Sabli, Ira K. D., Hodeib, Stephanie, Korol, Cecilia, Bilguvar, Kaya, Bolze, Alexandre, Bigio, Benedetta, Yang, Rui, Arias, Andrés Augusto, Zhou, Qinhua, Chbihi, Marwa, Bonnet-Madin, Lucie, Dorgham, Karim, Smith, Nikaïa, Schneider, William M., Razooky, Brandon S., Hoffmann, Hans-Heinrich, Michailidis, Eleftherios, Han, Jin Eun, Lorenzo, Lazaro, Bizien, Lucy, Meade, Philip, Neehus, Anna-Lena, Ugurbil, Aileen Camille, Kerner, Gaspard, Zhang, Peng, Rapaport, Franck, Manry, Jérémy, Masson, Cecile, Schlüter, Agatha, Le Voyer, Tom, Khan, Taushif, Fellay, Jacques, Roussel, Lucie, Alosaimi, Mohammed F., Al-Mulla, Fahd, Almourfi, Feras, Alsohime, Fahad, Al Turki, Saeed, Hasanato, Rana, Beek, Diederik van der, Bettini, Laura Rachele, Bonfanti, Paolo, Oler, Andrew J., Tompkins, Miranda F., Alba, Camille, Smits, Guillaume, Soler-Palacín, Pere, Martin-Nalda, Andrea, Colobran, Roger, Çölkesen, Fatma, Yasar, Kadriye Kart, Senoglu, Sevtap, Karabela, Şemsi Nur, Rodríguez-Gallego, Carlos, Novelli, Giuseppe, Tandjaoui-Lambiotte, Yacine, Laouénan, Cédric, Zhang, Q, Bastard, P, Liu, Z, Le Pen, J, Moncada-Velez, M, Chen, J, Ogishi, M, Sabli, I, Hodeib, S, Korol, C, Rosain, J, Bilguvar, K, Ye, J, Bolze, A, Bigio, B, Yang, R, Arias, A, Zhou, Q, Zhang, Y, Onodi, F, Korniotis, S, Karpf, L, Philippot, Q, Chbihi, M, Bonnet-Madin, L, Dorgham, K, Smith, N, Schneider, W, Razooky, B, Hoffmann, H, Michailidis, E, Moens, L, Han, J, Lorenzo, L, Bizien, L, Meade, P, Neehus, A, Ugurbil, A, Corneau, A, Kerner, G, Zhang, P, Rapaport, F, Seeleuthner, Y, Manry, J, Masson, C, Schmitt, Y, Schlüter, A, Le Voyer, T, Khan, T, Li, J, Fellay, J, Roussel, L, Shahrooei, M, Alosaimi, M, Mansouri, D, Al-Saud, H, Al-Mulla, F, Almourfi, F, Al-Muhsen, S, Alsohime, F, Al Turki, S, Hasanato, R, van de Beek, D, Biondi, A, Bettini, L, D'Angio, M, Bonfanti, P, Imberti, L, Sottini, A, Paghera, S, Quiros-Roldan, E, Rossi, C, Oler, A, Tompkins, M, Alba, C, Vandernoot, I, Goffard, J, Smits, G, Migeotte, I, Haerynck, F, Soler-Palacin, P, Martin-Nalda, A, Colobran, R, Morange, P, Keles, S, Çölkesen, F, Ozcelik, T, Yasar, K, Senoglu, S, Karabela, Ş, Gallego, C, Novelli, G, Hraiech, S, Tandjaoui-Lambiotte, Y, Duval, X, Laouénan, C, Snow, A, Dalgard, C, Milner, J, Vinh, D, Mogensen, T, Marr, N, Spaan, A, Boisson, B, Boisson-Dupuis, S, Bustamante, J, Puel, A, Ciancanelli, M, Meyts, I, Maniatis, T, Soumelis, V, Amara, A, Nussenzweig, M, García-Sastre, A, Krammer, F, Pujol, A, Duffy, D, Lifton, R, Zhang, S, Gorochov, G, Béziat, V, Jouanguy, E, Sancho-Shimizu, V, Rice, C, Abel, L, Notarangelo, L, Cobat, A, Su, H, Casanova, J, Pesci, A, Neurology, AII - Infectious diseases, ANS - Neuroinfection & -inflammation, Infectious diseases, ACS - Pulmonary hypertension & thrombosis, Intensive Care Medicine, ACS - Heart failure & arrhythmias, Anesthesiology, ACS - Diabetes & metabolism, ACS - Microcirculation, UKRI Future Leader's Fellowship, Internal medicine, Pulmonary medicine, Intensive care medicine, Pathology, Medical Microbiology and Infection Prevention, Amsterdam Reproduction & Development (AR&D), Amsterdam Neuroscience - Neuroinfection & -inflammation, Laboratory Medicine, APH - Quality of Care, COVID-STORM Clinicians, COVID Clinicians, Imagine COVID Group, French COVID Cohort Study Group, CoV-Contact Cohort, Amsterdam UMC Covid-19 Biobank, COVID Human Genetic Effort, NIAID-USUHS/TAGC COVID Immunity Group, Foti, G., Bellani, G., Citerio, G., Contro, E., Pesci, A., Valsecchi, M.G., Cazzaniga, M., Abad, J., Aguilera-Albesa, S., Akcan, O.M., Darazam, I.A., Aldave, J.C., Ramos, M.A., Nadji, S.A., Alkan, G., Allardet-Servent, J., Allende, L.M., Alsina, L., Alyanakian, M.A., Amador-Borrero, B., Amoura, Z., Antolí, A., Arslan, S., Assant, S., Auguet, T., Azot, A., Bajolle, F., Baldolli, A., Ballester, M., Feldman, H.B., Barrou, B., Beurton, A., Bilbao, A., Blanchard-Rohner, G., Blanco, I., Blandinières, A., Blazquez-Gamero, D., Bloomfield, M., Bolivar-Prados, M., Borie, R., Bosteels, C., Bousfiha, A.A., Bouvattier, C., Boyarchuk, O., Bueno, MRP, Bustamante, J., Cáceres Agra, J.J., Calimli, S., Capra, R., Carrabba, M., Casasnovas, C., Caseris, M., Castelle, M., Castelli, F., de Vera, M.C., Castro, M.V., Catherinot, E., Chalumeau, M., Charbit, B., Cheng, M.P., Clavé, P., Clotet, B., Codina, A., Colkesen, F., Çölkesen, F., Colobran, R., Comarmond, C., Dalmau, D., Darley, D.R., Dauby, N., Dauger, S., de Pontual, L., Dehban, A., Delplancq, G., Demoule, A., Diehl, J.L., Dobbelaere, S., Durand, S., Eldars, W., Elgamal, M., Elnagdy, M.H., Emiroglu, M., Erdeniz, E.H., Aytekin, S.E., Euvrard, R., Evcen, R., Fabio, G., Faivre, L., Falck, A., Fartoukh, M., Faure, M., Arquero, M.F., Flores, C., Francois, B., Fumadó, V., Fusco, F., Solis, B.G., Gaussem, P., Gil-Herrera, J., Gilardin, L., Alarcon, M.G., Girona-Alarcón, M., Goffard, J.C., Gok, F., González-Montelongo, R., Guerder, A., Gul, Y., Guner, S.N., Gut, M., Hadjadj, J., Haerynck, F., Halwani, R., Hammarström, L., Hatipoglu, N., Hernandez-Brito, E., Heijmans, C., Holanda-Peña, M.S., Horcajada, J.P., Hoste, L., Hoste, E., Hraiech, S., Humbert, L., Iglesias, A.D., Íñigo-Campos, A., Jamme, M., Arranz, M.J., Jordan, I., Jorens, P., Kanat, F., Kapakli, H., Kara, I., Karbuz, A., Yasar, K.K., Keles, S., Demirkol, Y.K., Klocperk, A., Król, Z.J., Kuentz, P., Kwan, YWM, Lagier, J.C., Lambrecht, B.N., Lau, Y.L., Le Bourgeois, F., Leo, Y.S., Lopez, R.L., Leung, D., Levin, M., Levy, M., Lévy, R., Li, Z., Linglart, A., Loeys, B., Lorenzo-Salazar, J.M., Louapre, C., Lubetzki, C., Luyt, C.E., Lye, D.C., Mansouri, D., Marjani, M., Pereira, J.M., Martin, A., Pueyo, D.M., Martinez-Picado, J., Marzana, I., Mathian, A., Matos, LRB, Matthews, G.V., Mayaux, J., Mège, J.L., Melki, I., Meritet, J.F., Metin, O., Meyts, I., Mezidi, M., Migeotte, I., Millereux, M., Mirault, T., Mircher, C., Mirsaeidi, M., Melián, A.M., Martinez, A.M., Morange, P., Mordacq, C., Morelle, G., Mouly, S., Muñoz-Barrera, A., Naesens, L., Nafati, C., Neves, J.F., Ng, LFP, Medina, Y.N., Cuadros, E.N., Ocejo-Vinyals, J.G., Orbak, Z., Oualha, M., Özçelik, T., Pan-Hammarström, Q., Parizot, C., Pascreau, T., Paz-Artal, E., Pellegrini, S., de Diego, R.P., Philippe, A., Philippot, Q., Planas-Serra, L., Ploin, D., Poissy, J., Poncelet, G., Pouletty, M., Quentric, P., Raoult, D., Rebillat, A.S., Reisli, I., Ricart, P., Richard, J.C., Rivet, N., Rivière, J.G., Blanch, G.R., Rodrigo, C., Rodriguez-Gallego, C., Rodríguez-Palmero, A., Romero, C.S., Rothenbuhler, A., Rozenberg, F., Ruiz Del Prado, M.Y., Riera, J.S., Sanchez, O., Sánchez-Ramón, S., Schluter, A., Schmidt, M., Schweitzer, C.E., Scolari, F., Sediva, A., Seijo, L.M., Sene, D., Senoglu, S., Seppänen, MRJ, Ilovich, A.S., Shahrooei, M., Slabbynck, H., Smadja, D.M., Sobh, A., Moreno, X.S., Solé-Violán, J., Soler, C., Soler-Palacín, P., Stepanovskiy, Y., Stoclin, A., Taccone, F., Tandjaoui-Lambiotte, Y., Taupin, J.L., Tavernier, S.J., Terrier, B., Thumerelle, C., Tomasoni, G., Toubiana, J., Alvarez, J.T., Trouillet-Assant, S., Troya, J., Tucci, A., Ursini, M.V., Uzunhan, Y., Vabres, P., Valencia-Ramos, J., Van Braeckel, E., Van de Velde, S., Van Den Rym, A.M., Van Praet, J., Vandernoot, I., Vatansev, H., Vélez-Santamaria, V., Viel, S., Vilain, C., Vilaire, M.E., Vincent, A., Voiriot, G., Vuotto, F., Yosunkaya, A., Young, B.E., Yucel, F., Zannad, F., Zatz, M., Belot, A., Bole-Feysot, C., Lyonnet, S., Masson, C., Nitschke, P., Pouliet, A., Schmitt, Y., Tores, F., Zarhrate, M., Abel, L., Andrejak, C., Angoulvant, F., Bachelet, D., Basmaci, R., Behillil, S., Beluze, M., Benkerrou, D., Bhavsar, K., Bompart, F., Bouadma, L., Bouscambert, M., Caralp, M., Cervantes-Gonzalez, M., Chair, A., Coelho, A., Couffignal, C., Couffin-Cadiergues, S., D'Ortenzio, E., Da Silveira, C., Debray, M.P., Deplanque, D., Descamps, D., Desvallées, M., Diallo, A., Diouf, A., Dorival, C., Dubos, F., Duval, X., Eloy, P., Enouf, V.V., Esperou, H., Esposito-Farese, M., Etienne, M., Ettalhaoui, N., Gault, N., Gaymard, A., Ghosn, J., Gigante, T., Gorenne, I., Guedj, J., Hoctin, A., Hoffmann, I., Jaafoura, S., Kafif, O., Kaguelidou, F., Kali, S., Khalil, A., Khan, C., Laouénan, C., Laribi, S., Le, M., Le Hingrat, Q., Le Mestre, S., Le Nagard, H., Lescure, F.X., Lévy, Y., Levy-Marchal, C., Lina, B., Lingas, G., Lucet, J.C., Malvy, D., Mambert, M., Mentré, F., Mercier, N., Meziane, A., Mouquet, H., Mullaert, J., Neant, N., Noret, M., Pages, J., Papadopoulos, A., Paul, C., Peiffer-Smadja, N., Petrov-Sanchez, V., Peytavin, G., Picone, O., Puéchal, O., Rosa-Calatrava, M., Rossignol, B., Rossignol, P., Roy, C., Schneider, M., Semaille, C., Mohammed, N.S., Tagherset, L., Tardivon, C., Tellier, M.C., Téoulé, F., Terrier, O., Timsit, J.F., Trioux, T., Tual, C., Tubiana, S., van der Werf, S., Vanel, N., Veislinger, A., Visseaux, B., Wiedemann, A., Yazdanpanah, Y., Alavoine, L., Amat, KKA, Bielicki, J., Bruijning, P., Burdet, C., Caumes, E., Charpentier, C., Coignard, B., Costa, Y., Damond, F., Dechanet, A., Delmas, C., Ecobichon, J.L., Enouf, V., Espérou, H., Frezouls, W., Houhou, N., Ilic-Habensus, E., Kikoine, J., Lebeaux, D., Leclercq, A., Lehacaut, J., Letrou, S., Manchon, P., Mandic, M., Meghadecha, M., Motiejunaite, J., Nouroudine, M., Piquard, V., Postolache, A., Quintin, C., Rexach, J., Roufai, L., Terzian, Z., Thy, M., Vignali, V., van Agtmael, M., Algera, A.G., van Baarle, F., Bax, D., Beudel, M., Bogaard, H.J., Bomers, M., Bos, L., Botta, M., de Brabander, J., de Bree, G., Brouwer, M.C., de Bruin, S., Bugiani, M., Bulle, E., Chouchane, O., Cloherty, A., Elbers, P., Fleuren, L., Geerlings, S., Geerts, B., Geijtenbeek, T., Girbes, A., Goorhuis, B., Grobusch, M.P., Hafkamp, F., Hagens, L., Hamann, J., Harris, V., Hemke, R., Hermans, S.M., Heunks, L., Hollmann, M.W., Horn, J., Hovius, J.W., de Jong, M.D., Koning, R., van Mourik, N., Nellen, J., Paulus, F., Peters, E., van der Poll, T., Preckel, B., Prins, J.M., Raasveld, J., Reijnders, T., Schinkel, M., Schultz, M.J., Schuurman, A., Sigaloff, K., Smit, M., Stijnis, C.S., Stilma, W., Teunissen, C., Thoral, P., Tsonas, A., van der Valk, M., Veelo, D., Vlaar, APJ, de Vries, H., van Vugt, M., Wiersinga, W.J., Wouters, D., Zwinderman, AHK, van de Beek, D., Aiuti, A., Al Muhsen, S., Al-Mulla, F., Anderson, M.S., Arias, A.A., Bogunovic, D., Bolze, A., Bondarenko, A., Brodin, P., Bryceson, Y., Bustamante, C.D., Butte, M., Casari, G., Chakravorty, S., Christodoulou, J., Cirulli, E., Condino-Neto, A., Cooper, M.A., Dalgard, C.L., David, A., DeRisi, J.L., Desai, M., Drolet, B.A., Espinosa, S., Fellay, J., Franco, J.L., Gregersen, P.K., Hagin, D., Heath, J., Henrickson, S.E., Hsieh, E., Imai, K., Itan, Y., Karamitros, T., Kisand, K., Ku, C.L., Ling, Y., Lucas, C.L., Maniatis, T., Marodi, L., Milner, J., Mironska, K., Mogensen, T., Morio, T., Notarangelo, L.D., Novelli, A., Novelli, G., O'Farrelly, C., Okada, S., Ozcelik, T., Planas, A.M., Prando, C., Pujol, A., Quintana-Murci, L., Renia, L., Renieri, A., 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S., Tellier, M. -C., Timsit, J. -F., Teoule, F., Puechal, O., Desvallees, M., Enouf, V. V. E., Levy, Y., Ecobichon, J. -L., Amat, K. K. A., Lucet, J. -C., Grobusch, M. P., Hermans, S. M., Hovius, J. W., Prins, J. M., Stijnis, C. S., Joost Wiersinga, W., Algera, A. G., Schultz, M. J., Brouwer, M. C., Bogaard, H. J., Hollmann, M. W., de Jong, M. D., Vlaar, A. P. J., Zwinderman, A. H., Muhsen, S. A., Anderson, M. S., Barrett, K. S., Bustamante, C. D., Cooper, M. A., Derisi, J. L., Drolet, B. A., Franco, J. L., Gregersen, P. K., Henrickson, S. E., Ku, C. -L., Lucas, C. L., Planas, A. M., Uddin, M. J., Vazquez, S. E., Chauvin, S. D., Luthers, C. R., Bauman, B. M., Hupalo, D. M., Wilkerson, M. D., Zhang, Qian [0000-0002-9040-3289], Bastard, Paul [0000-0002-5926-8437], Le Pen, Jeremie [0000-0001-7025-9526], Moncada-Velez, Marcela [0000-0002-3073-5345], Ogishi, Masato [0000-0003-2421-7389], Sabli, Ira K. D. [0000-0002-0170-2990], Hodeib, Stephanie [0000-0002-5978-6189], Korol, Cecilia [0000-0002-0023-8823], Bilguvar, Kaya [0000-0002-7313-7652], Bolze, Alexandre [0000-0001-7399-2766], Bigio, Benedetta [0000-0001-7291-5638], Yang, Rui [0000-0003-4427-2158], Arias, Andrés Augusto [0000-0002-9478-8403], Zhou, Qinhua [0000-0002-5112-3727], Chbihi, Marwa [0000-0002-2771-851X], Bonnet-Madin, Lucie [0000-0002-9848-3287], Dorgham, Karim [0000-0001-9539-3203], Smith, Nikaïa [0000-0002-0202-612X], Schneider, William M. [0000-0001-9407-6118], Razooky, Brandon S. [0000-0002-5263-1512], Hoffmann, Hans-Heinrich [0000-0003-0554-0244], Michailidis, Eleftherios [0000-0002-9907-4346], Han, Jin Eun [0000-0003-1112-9320], Lorenzo, Lazaro [0000-0001-6648-8684], Bizien, Lucy [0000-0001-9163-9122], Meade, Philip [0000-0002-6754-7209], Neehus, Anna-Lena [0000-0002-8573-6820], Ugurbil, Aileen Camille [0000-0002-9450-3092], Kerner, Gaspard [0000-0003-0146-9428], Zhang, Peng [0000-0002-6129-567X], Rapaport, Franck [0000-0001-6553-2110], Manry, Jérémy [0000-0001-5998-2051], Masson, Cecile [0000-0001-7870-7821], Schlüter, Agatha [0000-0001-6732-1528], Le Voyer, Tom [0000-0002-0630-8626], Khan, Taushif [0000-0002-7917-8965], Fellay, Jacques [0000-0002-8240-939X], Roussel, Lucie [0000-0001-5355-702X], Alosaimi, Mohammed F. [0000-0002-8025-3491], Al-Mulla, Fahd [0000-0001-5409-3829], Almourfi, Feras [0000-0002-5166-4662], Alsohime, Fahad [0000-0002-4979-3895], Al Turki, Saeed [0000-0001-7017-336X], Hasanato, Rana [0000-0002-4697-2222], Beek, Diederik van der [0000-0002-4571-044X], Bettini, Laura Rachele [0000-0002-0280-1704], Bonfanti, Paolo [0000-0001-7289-8823], Oler, Andrew J. [0000-0002-6310-0434], Tompkins, Miranda F. [0000-0003-2941-7515], Alba, Camille [0000-0002-0458-1629], Smits, Guillaume [0000-0003-2845-6758], Soler-Palacín, Pere [0000-0002-0346-5570], Martin-Nalda, Andrea [0000-0002-3590-0186], Colobran, Roger [0000-0002-5964-536X], Çölkesen, Fatma [0000-0001-9545-5179], Yasar, Kadriye Kart [0000-0003-2963-4894], Senoglu, Sevtap [0000-0003-4796-9583], Karabela, Şemsi Nur [0000-0003-2562-3004], Rodríguez-Gallego, Carlos [0000-0002-4344-8644], Novelli, Giuseppe [0000-0002-7781-602X], Tandjaoui-Lambiotte, Yacine [0000-0003-1123-4788], and Laouénan, Cédric [0000-0002-3681-6314]
Subjects: Male, COVID19, Interferon Regulatory Factor-7, [SDV]Life Sciences [q-bio], NF-KAPPA-B, Receptor, Interferon alpha-beta, SUSCEPTIBILITY, susceptibility, Interferon alpha-beta, CoV-Contact Cohort, 0302 clinical medicine, Interferon, Loss of Function Mutation, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, 80 and over, Medicine and Health Sciences, Viral, Online, Imagine COVID Group, Child, Adolescent, Adult, Aged, Aged, 80 and over, Alleles, Asymptomatic Infections, Betacoronavirus, COVID-19, Child, Preschool, Coronavirus Infections/genetics, Coronavirus Infections/immunology, Female, Genetic Loci, Genetic Predisposition to Disease, Humans, Infant, Interferon Regulatory Factor-7/deficiency, Interferon Regulatory Factor-7/genetics, Interferon Type I/immunology, Middle Aged, Pandemics, Pneumonia, Viral/genetics, Pneumonia, Viral/immunology, Receptor, Interferon alpha-beta/deficiency, Receptor, Interferon alpha-beta/genetics, SARS-CoV-2, Toll-Like Receptor 3/deficiency, Toll-Like Receptor 3/genetics, Young Adult, Research Articles, 0303 health sciences, Multidisciplinary, COVID Clinicians, deficiency, 3. Good health, Multidisciplinary Sciences, DEFICIENCY, Settore MED/03, 030220 oncology & carcinogenesis, Interferon Type I, Science & Technology - Other Topics, medicine.symptom, Coronavirus Infections, Receptor, medicine.drug, NIAID-USUHS, Research Article, General Science & Technology, HERPES-SIMPLEX ENCEPHALITIS, French COVID Cohort Study Group, Pneumonia, Viral, Immunology, Asymptomatic, Virus, 03 medical and health sciences, Immunity, nf-kappa-b, medicine, Genetics, Preschool, COVID Human Genetic Effort, 030304 developmental biology, Biobank, Science & Technology, business.industry, R-Articles, TAGC COVID Immunity Group, Médecine pathologie humaine, herpes-simplex encephalitis, Pneumonia, Amsterdam UMC Covid-19, medicine.disease, COVID-STORM Clinicians, Toll-Like Receptor 3, 3121 General medicine, internal medicine and other clinical medicine, IRF7, 3111 Biomedicine, business, Interferon type I, Interferon regulatory factors
Abstract: COVID-STORM Clinicians Giuseppe Foti1, Giacomo Bellani 1, Giuseppe Citerio1, Ernesto Contro1, Alberto Pesci2, Maria Grazia Valsecchi3, Marina Cazzaniga4 1Department of Emergency, Anesthesia and Intensive Care, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 2Department of Pneumology, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 3Center of Bioinformatics and Biostatistics, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza, Italy. 4Phase I Research Center, School of Medicine and Surgery, University of Milano-Bicocca, San Gerardo Hospital, Monza IT, COVID Clinicians Jorge Abad1, Sergio Aguilera-Albesa2, Ozge Metin Akcan3, Ilad Alavi Darazam4, Juan C. Aldave5, Miquel Alfonso Ramos6, Seyed Alireza Nadji7, Gulsum Alkan8, Jerome Allardet-Servent9, Luis M. Allende10, Laia Alsina11, Marie-Alexandra Alyanakian12, Blanca Amador-Borrero13, Zahir Amoura14, Arnau Antolí15, Sevket Arslan16, Sophie Assant17, Terese Auguet18, Axelle Azot19, Fanny Bajolle20, Aurélie Baldolli21, Maite Ballester22, Hagit Baris Feldman23, Benoit Barrou24, Alexandra Beurton25, Agurtzane Bilbao26, Geraldine Blanchard-Rohner27, Ignacio Blanco1, Adeline Blandinières28, Daniel Blazquez-Gamero29, Marketa Bloomfield30, Mireia Bolivar-Prados31, Raphael Borie32, Cédric Bosteels33, Ahmed A. Bousfiha34, Claire Bouvattier35, Oksana Boyarchuk36, Maria Rita P. Bueno37, Jacinta Bustamante20, Juan José Cáceres Agra38, Semra Calimli39, Ruggero Capra40, Maria Carrabba41, Carlos Casasnovas42, Marion Caseris43, Martin Castelle44, Francesco Castelli45, Martín Castillo de Vera46, Mateus V. Castro37, Emilie Catherinot47, Martin Chalumeau48, Bruno Charbit49, Matthew P. Cheng50, Père Clavé31, Bonaventura Clotet51, Anna Codina52, Fatih Colkesen53, Fatma Çölkesen54, Roger Colobran55, Cloé Comarmond56, David Dalmau57, David Ross Darley58, Nicolas Dauby59, Stéphane Dauger60, Loic de Pontual61, Amin Dehban62, Geoffroy Delplancq63, Alexandre Demoule64, Jean-Luc Diehl65, Stephanie Dobbelaere66, Sophie Durand67, Waleed Eldars68, Mohamed Elgamal69, Marwa H. Elnagdy70, Melike Emiroglu71, Emine Hafize Erdeniz72, Selma Erol Aytekin73, Romain Euvrard74, Recep Evcen75, Giovanna Fabio41, Laurence Faivre76, Antonin Falck43, Muriel Fartoukh77, Morgane Faure78, Miguel Fernandez Arquero79, Carlos Flores80, Bruno Francois81, Victoria Fumadó82, Francesca Fusco83, Blanca Garcia Solis84, Pascale Gaussem85, Juana Gil-Herrera86, Laurent Gilardin87, Monica Girona Alarcon88, Mònica Girona-Alarcón88, Jean-Christophe Goffard89, Funda Gok90, Rafaela González-Montelongo91, Antoine Guerder92, Yahya Gul93, Sukru Nail Guner93, Marta Gut94, Jérôme Hadjadj95, Filomeen Haerynck96, Rabih Halwani97, Lennart Hammarström98, Nevin Hatipoglu99, Elisa Hernandez-Brito100, Cathérine Heijmans101, María Soledad Holanda-Peña102, Juan Pablo Horcajada103, Levi Hoste104, Eric Hoste105, Sami Hraiech106, Linda Humbert107, Alejandro D. Iglesias108, Antonio Íñigo-Campos91, Matthieu Jamme109, María Jesús Arranz110, Iolanda Jordan111, Philippe Jorens112, Fikret Kanat113, Hasan Kapakli114, Iskender Kara115, Adem Karbuz116, Kadriye Kart Yasar117, Sevgi Keles118, Yasemin Kendir Demirkol119, Adam Klocperk120, Zbigniew J. Król121, Paul Kuentz122, Yat Wah M. Kwan123, Jean-Christophe Lagier124, Bart N. Lambrecht33, Yu-Lung Lau125, Fleur Le Bourgeois60, Yee-Sin Leo126, Rafael Leon Lopez127, Daniel Leung125, Michael Levin128, Michael Levy60, Romain Lévy20, Zhi Li49, Agnes Linglart129, Bart Loeys130, José M. Lorenzo-Salazar91, Céline Louapre131, Catherine Lubetzki131, Charles-Edouard Luyt132, David C. Lye133, Davood Mansouri134, Majid Marjani135, Jesus Marquez Pereira136, Andrea Martin137, David Martínez Pueyo138, Javier Martinez-Picado139, Iciar Marzana140, Alexis Mathian14, Larissa R. B. Matos37, Gail V. Matthews141, Julien Mayaux142, Jean-Louis Mège143, Isabelle Melki144, Jean-François Meritet145, Ozge Metin146, Isabelle Meyts147, Mehdi Mezidi148, Isabelle Migeotte149, Maude Millereux150, Tristan Mirault151, Clotilde Mircher67, Mehdi Mirsaeidi152, Abián Montesdeoca Melián153, Antonio Morales Martinez154, Pierre Morange155, Clémence Mordacq107, Guillaume Morelle156, Stéphane Mouly13, Adrián Muñoz-Barrera91, Leslie Naesens157, Cyril Nafati158, João Farela Neves159, Lisa FP. Ng160, Yeray Novoa Medina161, Esmeralda Nuñez Cuadros162, J. Gonzalo Ocejo-Vinyals163, Zerrin Orbak164, Mehdi Oualha20, Tayfun Özçelik165, Qiang Pan-Hammarström166, Christophe Parizot142, Tiffany Pascreau167, Estela Paz-Artal168, Sandra Pellegrini49, Rebeca Pérez de Diego84, Aurélien Philippe169, Quentin Philippot77, Laura Planas-Serra170, Dominique Ploin171, Julien Poissy172, Géraldine Poncelet43, Marie Pouletty173, Paul Quentric142, Didier Raoult143, Anne-Sophie Rebillat67, Ismail Reisli174, Pilar Ricart175, Jean-Christophe Richard176, Nadia Rivet28, Jacques G. Rivière177, Gemma Rocamora Blanch15, Carlos Rodrigo1, Carlos Rodriguez-Gallego178, Agustí Rodríguez-Palmero179, Carolina Soledad Romero180, Anya Rothenbuhler181, Flore Rozenberg182, Maria Yolanda Ruiz del Prado183, Joan Sabater Riera15, Oliver Sanchez184, Silvia Sánchez-Ramón185, Agatha Schluter170, Matthieu Schmidt186, Cyril E. Schweitzer187, Francesco Scolari188, Anna Sediva189, Luis M. Seijo190, Damien Sene13, Sevtap Senoglu117, Mikko R. J. Seppänen191, Alex Serra Ilovich192, Mohammad Shahrooei62, Hans Slabbynck193, David M. Smadja194, Ali Sobh195, Xavier Solanich Moreno15, Jordi Solé-Violán196, Catherine Soler197, Pere Soler-Palacín137, Yuri Stepanovskiy198, Annabelle Stoclin199, Fabio Taccone149, Yacine Tandjaoui-Lambiotte200, Jean-Luc Taupin201, Simon J. Tavernier202, Benjamin Terrier203, Caroline Thumerelle107, Gabriele Tomasoni204, Julie Toubiana48, Josep Trenado Alvarez205, Sophie Trouillet-Assant206, Jesús Troya207, Alessandra Tucci208, Matilde Valeria Ursini‬83, Yurdagul Uzunhan209, Pierre Vabres210, Juan Valencia-Ramos211, Eva Van Braeckel33, Stijn Van de Velde212, Ana Maria Van Den Rym84, Jens Van Praet213, Isabelle Vandernoot214, Hulya Vatansev215, Valentina Vélez-Santamaria42, Sébastien Viel171, Cédric Vilain216, Marie E. Vilaire67, Audrey Vincent35, Guillaume Voiriot217, Fanny Vuotto107, Alper Yosunkaya90, Barnaby E. Young126, Fatih Yucel218, Faiez Zannad219, Mayana Zatz37, Alexandre Belot220*, Imagine COVID Group Christine Bole-Feysot, Stanislas Lyonnet*, Cécile Masson, Patrick Nitschke, Aurore Pouliet, Yoann Schmitt, Frederic Tores, Mohammed Zarhrate Imagine Institute, Université de Paris, INSERM UMR 1163, Paris, France. *Leader of the Imagine COVID Group., French COVID Cohort Study Group Laurent Abel1, Claire Andrejak2, François Angoulvant3, Delphine Bachelet4, Romain Basmaci5, Sylvie Behillil6, Marine Beluze7, Dehbia Benkerrou8, Krishna Bhavsar4, François Bompart9, Lila Bouadma4, Maude Bouscambert10, Mireille Caralp11, Minerva Cervantes-Gonzalez12, Anissa Chair4, Alexandra Coelho13, Camille Couffignal4, Sandrine Couffin-Cadiergues14, Eric D’Ortenzio12, Charlene Da Silveira4, Marie-Pierre Debray4, Dominique Deplanque15, Diane Descamps16, Mathilde Desvallées17, Alpha Diallo18, Alphonsine Diouf13, Céline Dorival8, François Dubos19, Xavier Duval4, Philippine Eloy4, Vincent VE Enouf20, Hélène Esperou21, Marina Esposito-Farese4, Manuel Etienne22, Nadia Ettalhaoui4, Nathalie Gault4, Alexandre Gaymard10, Jade Ghosn4, Tristan Gigante23, Isabelle Gorenne4, Jérémie Guedj24, Alexandre Hoctin13, Isabelle Hoffmann4, Salma Jaafoura21, Ouifiya Kafif4, Florentia Kaguelidou25, Sabina Kali4, Antoine Khalil4, Coralie Khan17, Cédric Laouénan4, Samira Laribi4, Minh Le4, Quentin Le Hingrat4, Soizic Le Mestre18, Hervé Le Nagard24, François-Xavier Lescure4, Yves Lévy26, Claire Levy-Marchal27, Bruno Lina10, Guillaume Lingas24, Jean Christophe Lucet4, Denis Malvy28, Marina Mambert13, France Mentré4, Noémie Mercier18, Amina Meziane8, Hugo Mouquet20, Jimmy Mullaert4, Nadège Neant24, Marion Noret29, Justine Pages30, Aurélie Papadopoulos21, Christelle Paul18, Nathan Peiffer-Smadja4, Ventzislava Petrov-Sanchez18, Gilles Peytavin4, Olivier Picone31, Oriane Puéchal12, Manuel Rosa-Calatrava10, Bénédicte Rossignol23, Patrick Rossignol32, Carine Roy4, Marion Schneider4, Caroline Semaille12, Nassima Si Mohammed4, Lysa Tagherset4, Coralie Tardivon4, Marie-Capucine Tellier4, François Téoulé8, Olivier Terrier10, Jean-François Timsit4, Théo Trioux4, Christelle Tual33, Sarah Tubiana4, Sylvie van der Werf34, Noémie Vanel35, Aurélie Veislinger33, Benoit Visseaux16, Aurélie Wiedemann26, Yazdan Yazdanpanah36 1Inserm UMR 1163, Paris, France. 2CHU Amiens, France. 3Hôpital Necker, Paris, France. 4Hôpital Bichat, Paris, France. 5Hôpital Louis Mourrier, Colombes, France. 6Institut Pasteur, Paris, France. 7F-CRIN Partners Platform, AP-HP, Université de Paris, Paris, France. 8Inserm UMR 1136, Paris, France. 9Drugs for Neglected Diseases Initiative, Geneva, Switzerland. 10Inserm UMR 1111, Lyon, France. 11Inserm Transfert, Paris, France. 12REACTing, Paris, France. 13Inserm UMR 1018, Paris, France. 14Inserm, Pôle Recherche Clinique, Paris, France. 15CIC 1403 Inserm-CHU Lille, Paris, France. 16Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 17Inserm UMR 1219, Bordeaux, France. 18ANRS, Paris, France. 19CHU Lille, Lille, France. 20Pasteur Institute, Paris, France. 21Inserm sponsor, Paris, France. 22CHU Rouen–SMIT, Rouen, France. 23FCRIN INI-CRCT, Nancy, France. 24Inserm UMR 1137, Paris, France. 25Centre d’Investigation Clinique, Inserm CIC1426, Hôpital Robert Debré, Paris, France. 26Inserm UMR 955, Créteil, France; Vaccine Research Instiute (VRI), Paris, France. 27F-CRIN INI-CRCT, Paris, France. 28CHU de Bordeaux–SMIT, Bordeaux, France. 29RENARCI, Annecy, France. 30Hôpital Robert Debré, Paris, France. 31Hôpital Louis Mourier–Gynécologie, Colombes, France. 32University of Lorraine, Plurithematic Clinical Investigation Centre Inserm CIC-P; 1433, Inserm U1116, CHRU Nancy Hopitaux de Brabois, F-CRIN INI-CRCT (Cardiovascular and Renal Clinical Trialists), Nancy, France. 33Inserm CIC-1414, Rennes, France. 34Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 35Hôpital la Timone, Marseille, France. 36Bichat–SMIT, Paris, France., CoV-Contact Cohort Loubna Alavoine1, Karine K. A. Amat2, Sylvie Behillil3, Julia Bielicki4, Patricia Bruijning5, Charles Burdet6, Eric Caumes7, Charlotte Charpentier8, Bruno Coignard9, Yolande Costa1, Sandrine Couffin-Cadiergues10, Florence Damond8, Aline Dechanet11, Christelle Delmas10, Diane Descamps8, Xavier Duval1, Jean-Luc Ecobichon1, Vincent Enouf3, Hélène Espérou10, Wahiba Frezouls1, Nadhira Houhou11, Emila Ilic-Habensus1, Ouifiya Kafif11, John Kikoine11, Quentin Le Hingrat8, David Lebeaux12, Anne Leclercq1, Jonathan Lehacaut1, Sophie Letrou1, Bruno Lina13, Jean-Christophe Lucet14, Denis Malvy15, Pauline Manchon11, Milica Mandic1, Mohamed Meghadecha16, Justina Motiejunaite17, Mariama Nouroudine1, Valentine Piquard11, Andreea Postolache11, Caroline Quintin1, Jade Rexach1, Layidé Roufai10, Zaven Terzian11, Michael Thy18, Sarah Tubiana1, Sylvie van der Werf3, Valérie Vignali1, Benoit Visseaux8, Yazdan Yazdanpanah14 1Centre d’Investigation Clinique, Inserm CIC 1425, Hôpital Bichat Claude Bernard, APHP, Paris, France. 2IMEA Fondation Léon M’Ba, Paris, France. 3Institut Pasteur, UMR 3569 CNRS, Université de Paris, Paris, France. 4University of Basel Children’s Hospital. 5Julius Center for Health Sciences and Primary Care, Utrecht, Netherlands. 6Université de Paris, IAME, Inserm UMR 1137, F-75018, Paris, France, Hôpital Bichat Claude Bernard, APHP, Paris, France. 7Hôpital Pitiè Salpétriere, APHP, Paris. 8Université de Paris, IAME, INSERM UMR 1137, AP-HP, University Hospital Bichat Claude Bernard, Virology, Paris, France. 9Santé Publique France, Saint Maurice, France. 10Pole Recherche Clinique, Inserm, Paris, France. 11Hôpital Bichat Claude Bernard, APHP, Paris, France. 12APHP, Paris, France. 13Virpath Laboratory, International Center of Research in Infectiology, Lyon University, INSERM U1111, CNRS UMR 5308, ENS, UCBL, Lyon, France. 14IAME Inserm UMR 1138, Hôpital Bichat Claude Bernard, APHP, Paris, France. 15Service des Maladies Infectieuses et Tropicales; Groupe Pellegrin-Place Amélie-Raba-Léon, Bordeaux, France. 16Hôpital Hotel Dieu, APHP, Paris, France. 17Service des Explorations Fonctionnelles, Hôpital Bichat–Claude Bernard, APHP, Paris, France. 18Center for Clinical Investigation, Assistance Publique-Hôpitaux de Paris, Bichat-Claude Bernard University Hospital, Paris, France., Amsterdam UMC Covid-19 Biobank Michiel van Agtmael1, Anna Geke Algera2, Frank van Baarle2, Diane Bax3, Martijn Beudel4, Harm Jan Bogaard5, Marije Bomers1, Lieuwe Bos2, Michela Botta2, Justin de Brabander6, Godelieve de Bree6, Matthijs C. Brouwer4, Sanne de Bruin2, Marianna Bugiani7, Esther Bulle2, Osoul Chouchane1, Alex Cloherty3, Paul Elbers2, Lucas Fleuren2, Suzanne Geerlings1, Bart Geerts8, Theo Geijtenbeek9, Armand Girbes2, Bram Goorhuis1, Martin P. Grobusch1, Florianne Hafkamp9, Laura Hagens2, Jorg Hamann10, Vanessa Harris1, Robert Hemke11, Sabine M. Hermans1, Leo Heunks2, Markus W. Hollmann8, Janneke Horn2, Joppe W. Hovius1, Menno D. de Jong12, Rutger Koning4, Niels van Mourik2, Jeaninne Nellen1, Frederique Paulus2, Edgar Peters1, Tom van der Poll1, Benedikt Preckel8, Jan M. Prins1, Jorinde Raasveld2, Tom Reijnders1, Michiel Schinkel1, Marcus J. Schultz2, Alex Schuurman13, Kim Sigaloff1, Marry Smit2, Cornelis S. Stijnis1, Willemke Stilma2, Charlotte Teunissen14, Patrick Thoral2, Anissa Tsonas2, Marc van der Valk1, Denise Veelo8, Alexander P.J. Vlaar15, Heder de Vries2, Michèle van Vugt1, W. Joost Wiersinga1, Dorien Wouters16, A. H. (Koos) Zwinderman17, Diederik van de Beek4* 1Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 2Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 3Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 4Department of Neurology, Amsterdam UMC, Amsterdam Neuroscience, Amsterdam, Netherlands. 5Department of Pulmonology, Amsterdam UMC, Amsterdam, Netherlands. 6Department of Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands. 7Department of Pathology, Amsterdam UMC, Amsterdam, Netherlands. 8Department of Anesthesiology, Amsterdam UMC, Amsterdam, Netherlands. 9Department of Experimental Immunology, Amsterdam UMC, Amsterdam, Netherlands. 10Amsterdam UMC Biobank Core Facility, Amsterdam UMC, Amsterdam, Netherlands. 11Department of Radiology, Amsterdam UMC, Amsterdam, Netherlands. 12Department of Medical Microbiology, Amsterdam UMC, Amsterdam, Netherlands. 13Department of Internal Medicine, Amsterdam UMC, Amsterdam, Netherlands. 14Neurochemical Laboratory, Amsterdam UMC, Amsterdam, Netherlands. 15Department of Intensive Care, Amsterdam UMC, Amsterdam, Netherlands. 16Department of Clinical Chemistry, Amsterdam UMC, Amsterdam, Netherlands. 17Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, Amsterdam, Netherlands. 18Department of Neurology, Amsterdam UMC, Amsterdam, Netherlands. *Leader of the AMC Consortium., COVID Human Genetic Effort Laurent Abel1, Alessandro Aiuti2, Saleh Al Muhsen3, Fahd Al-Mulla4, Mark S. Anderson5, Andrés Augusto Arias6, Hagit Baris Feldman7, Dusan Bogunovic8, Alexandre Bolze9, Anastasiia Bondarenko10, Ahmed A. Bousfiha11, Petter Brodin12, Yenan Bryceson12, Carlos D. Bustamante13, Manish Butte14, Giorgio Casari15, Samya Chakravorty16, John Christodoulou17, Elizabeth Cirulli9, Antonio Condino-Neto18, Megan A. Cooper19, Clifton L. Dalgard20, Alessia David21, Joseph L. DeRisi22, Murkesh Desai23, Beth A. Drolet24, Sara Espinosa25, Jacques Fellay26, Carlos Flores27, Jose Luis Franco28, Peter K. Gregersen29, Filomeen Haerynck30, David Hagin31, Rabih Halwani32, Jim Heath33, Sarah E. Henrickson34, Elena Hsieh35, Kohsuke Imai36, Yuval Itan8, Timokratis Karamitros37, Kai Kisand38, Cheng-Lung Ku39, Yu-Lung Lau40, Yun Ling41, Carrie L. Lucas42, Tom Maniatis43, Davoud Mansouri44, Laszlo Marodi45, Isabelle Meyts46, Joshua Milner47, Kristina Mironska48, Trine Mogensen49, Tomohiro Morio50, Lisa FP. Ng51, Luigi D. Notarangelo52, Antonio Novelli53, Giuseppe Novelli54, Cliona O’Farrelly55, Satoshi Okada56, Tayfun Ozcelik57, Rebeca Perez de Diego58, Anna M. Planas59, Carolina Prando60, Aurora Pujol61, Lluis Quintana-Murci62, Laurent Renia63, Alessandra Renieri64, Carlos Rodríguez-Gallego65, Vanessa Sancho-Shimizu66, Vijay Sankaran67, Kelly Schiabor Barrett9, Mohammed Shahrooei68, Andrew Snow69, Pere Soler-Palacín70, András N. Spaan71, Stuart Tangye72, Stuart Turvey73, Furkan Uddin74, Mohammed J. Uddin75, Diederik van de Beek76, Sara E. Vazquez77, Donald C. Vinh78, Horst von Bernuth79, Nicole Washington9, Pawel Zawadzki80, Helen C. Su52, Jean-Laurent Casanova81 1INSERM U1163, University of Paris, Imagine Institute, Paris, France. 2San Raffaele Telethon Institute for Gene Therapy, IRCCS Ospedale San Raffaele, Milan, Italy. 3King Saud University, Riyadh, Saudi Arabia. 4Kuwait University, Kuwait City, Kuwait. 5University of California, San Francisco, San Francisco, CA, USA. 6Universidad de Antioquia, Group of Primary Immunodeficiencies, Antioquia, Colombia. 7The Genetics Institute, Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8Icahn School of Medicine at Mount Sinai, New York, NY, USA. 9Helix, San Mateo, CA, USA. 10Shupyk National Medical Academy for Postgraduate Education, Kiev, Ukraine. 11Clinical Immunology Unit, Pediatric Infectious Disease Departement, Faculty of Medicine and Pharmacy, Averroes University Hospital; LICIA Laboratoire d’Immunologie Clinique, d’Inflammation et d’Allergie, Hassann Ii University, Casablanca, Morocco. 12Karolinska Institute, Stockholm, Sweden. 13Stanford University, Stanford, CA, USA. 14University of California, Los Angeles, CA, USA. 15Medical Genetics, IRCCS Ospedale San Raffaele, Milan, Italy. 16Emory University Department of Pediatrics and Children’s Healthcare of Atlanta, Atlanta, GA, USA. 17Murdoch Children’s Research Institute, Victoria, Australia. 18University of São Paulo, São Paulo, Brazil. 19Washington University School of Medicine, St. Louis, MO, USA. 20The American Genome Center; Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 21Centre for Bioinformatics and System Biology, Department of Life Sciences, Imperial College London, South Kensington Campus, London, UK. 22University of California, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA, USA. 23Bai Jerbai Wadia Hospital for Children, Mumbai, India. 24School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 25Instituto Nacional de Pediatria (National Institute of Pediatrics), Mexico City, Mexico. 26Swiss Federal Institute of Technology Lausanne, Lausanne, Switzerland. 27Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Canarian Health System, Santa Cruz de Tenerife, Spain. 28University of Antioquia, Medellín, Colombia. 29Feinstein Institute for Medical Research, Northwell Health USA, Manhasset, NY, USA. 30Department of Paediatric Immunology and Pulmonology, Centre for Primary Immunodeficiency Ghent (CPIG), PID Research Lab, Jeffrey Modell Diagnosis and Research Centre, Ghent University Hospital, Edegem, Belgium. 31The Genetics Institute, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 32Sharjah Institute of Medical Research, College of Medicine, University of Sharjah, Sharjah, UAE. 33Institute for Systems Biology, Seattle, WA, USA. 34Children’s Hospital of Philadelphia, Philadelphia, PA, USA. 35Anschutz Medical Campus, Aurora, CO, USA. 36Riken, Tokyo, Japan. 37Hellenic Pasteur Institute, Athens, Greece. 38University of Tartu, Tartu, Estonia. 39Chang Gung University, Taoyuan County, Taiwan. 40The University of Hong Kong, Hong Kong, China. 41Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 42Yale School of Medicine, New Haven, CT, USA. 43New York Genome Center, New York, NY, USA. 44Shahid Beheshti University of Medical Sciences, Tehran, Iran. 45Semmelweis University Budapest, Budapest, Hungary. 46KU Leuven, Department of Immunology, Microbiology and Transplantation, Leuven, Belgium. 47Columbia University Medical Center, New York, NY, USA. 48University Clinic for Children’s Diseases, Skopje, North Macedonia. 49Aarhus University, Aarhus, Denmark. 50Tokyo Medical & Dental University Hospital, Tokyo, Japan. 51Singapore Immunology Network, Singapore. 52National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. 53Bambino Gesù Children’s Hospital, Rome, Italy. 54Department of Biomedicine and Prevention, University of Rome “Tor Vergata,” Rome, Italy. 55Trinity College, Dublin, Ireland. 56Hiroshima University, Hiroshima, Japan. 57Bilkent University, Ankara, Turkey. 58Laboratory of Immunogenetics of Human Diseases, Innate Immunity Group, IdiPAZ Institute for Health Research, La Paz Hospital, Madrid, Spain. 59IIBB-CSIC, IDIBAPS, Barcelona, Spain. 60Faculdades Pequeno Príncipe e Instituto de Pesquisa Pelé Pequeno Príncipe, Curitiba, Brazil. 61Neurometabolic Diseases Laboratory, IDIBELL–Hospital Duran I Reynals; Catalan Institution for Research and Advanced Studies (ICREA); CIBERER U759, ISCiii Madrid Spain, Barcelona, Spain. 62Institut Pasteur (CNRS UMR2000) and Collège de France, Paris, France. 63Infectious Diseases Horizontal Technology Center and Singapore Immunology Network, Agency for Science Technology (A*STAR), Singapore. 64Medical Genetics, University of Siena, Siena, Italy; Genetica Medica, Azienda Ospedaliero-Universitaria Senese, Italy; GEN-COVID Multicenter Study. 65Hospital Universitario de Gran Canaria Dr. Negrín, Canarian Health System, Canary Islands, Spain. 66Imperial College London, London, UK. 67Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA. 68Saeed Pathobiology and Genetic Lab, Tehran, Iran. 69Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 70Hospital Universitari Vall d’Hebron, Barcelona, Spain. 71University Medical Center Utrecht, Amsterdam, The Netherlands. 72Garvan Institute of Medical Research, Sydney, Australia. 73The University of British Columbia, Vancouver, Canada. 74Holy Family Red Crescent Medical College; Centre for Precision Therapeutics, NeuroGen Children’s Healthcare; Genetics and Genomic Medicine Centre, NeuroGen Children’s Healthcare, Dhaka, Bangladesh. 75Mohammed Bin Rashid University of Medicine and Health Sciences, College of Medicine, Dubai, UAE; The Centre for Applied Genomics, Department of Genetics and Genome Biology, The Hospital for Sick Children, Toronto, Ontario, Canada. 76Amsterdam UMC, University of Amsterdam, Department of Neurology, Amsterdam Neuroscience, Amsterdam, The Netherlands. 77University of California, San Francisco, CA, USA. 78McGill University Health Centre, Montreal, Canada. 79Charité–Berlin University Hospital Center, Berlin, Germany. 80Molecular Biophysics Division, Faculty of Physics, A. Mickiewicz University, Uniwersytetu Poznanskiego 2, Poznań, Poland. 81Rockefeller University, Howard Hughes Medical Institute, Necker Hospital, New York, NY, USA. *Leaders of the COVID Human Genetic Effort., NIAID-USUHS/TAGC COVID Immunity Group Huie Jing1,2, Wesley Tung1,2, Christopher R. Luthers3, Bradly M. Bauman3, Samantha Shafer2,4, Lixin Zheng2,4, Zinan Zhang2,4, Satoshi Kubo2,4, Samuel D. Chauvin2,4, Kazuyuki Meguro1,2, Elana Shaw1,2, Michael Lenardo2,4, Justin Lack5, Eric Karlins6, Daniel M. Hupalo7, John Rosenberger7, Gauthaman Sukumar7, Matthew D. Wilkerson7, Xijun Zhang7 1Laboratory of Clinical Immunology and Microbiology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 2NIAID Clinical Genomics Program, National Institutes of Health, Bethesda, MD, USA. 3Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA. 4Laboratory of Immune System Biology, Division of Intramural Research, NIAID, NIH, Bethesda, MD, USA. 5NIAID Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. 6Bioinformatics and Computational Biosciences Branch, Office of Cyber Infrastructure and Computational Biology, NIAID, NIH, Bethesda, MD, USA. 7The American Genome Center, Uniformed Services University of the Health Sciences, Bethesda, MD, USA., Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection., We thank the generous donation from Fisher Center for Alzheimer’s Research Foundation for our research. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH) (R01AI088364), the National Center for Advancing Translational Sciences (NCATS), NIH Clinical and Translational Science Award (CTSA) program (UL1 TR001866), a Fast Grant from Emergent Ventures, Mercatus Center at George Mason University, the Yale Center for Mendelian Genomics and the GSP Coordinating Center funded by the National Human Genome Research Institute (NHGRI) (UM1HG006504 and U24HG008956), the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (FRM) (EQU201903007798), the FRM and ANR GENCOVID project, ANRS-COV05, the Square Foundation, Grandir - Fonds de solidarité pour l’enfance, the SCOR Corporate Foundation for Science, Institut National de la Santé et de la Recherche Médicale (INSERM), the University of Paris. The French COVID Cohort study group was sponsored by Inserm and supported by the REACTing consortium and by a grant from the French Ministry of Health (PHRC 20-0424). Regione Lombardia, Italy (project “Risposta immune in pazienti con COVID-19 e co-morbidità”), and the Intramural Research Program of the NIAID, NIH. The laboratory of Genomes & Cell Biology of Disease is supported by “Integrative Biology of Emerging Infectious Diseases” (grant no. ANR-10-LABX-62-IBEID), the “Fondation pour la Recherche Medicale” (grant FRM - EQU202003010193), the “Agence Nationale de la Recherche” (ANR FLASH COVID project IDISCOVR cofounded by the “Fondation pour la Recherche Médicale”), University of Paris (“Plan de Soutien Covid-19”: RACPL20FIR01-COVID-SOUL). IM is a senior clinical investigator with the FWO Vlaanderen; IM and LM are supported by FWO G0C8517N – GOB5120N. The VS team was supported by “Agence Nationale de la Recherche” (ANR-17-CE15-0003, ANR-17-CE15-0003-01), and by Université de Paris “PLAN D’URGENCE COVID19”. LK was supported by a fellowship from the French Ministry of Research. VS-S is supported by a UKRI Future Leaders Fellowship (MR/S032304/1). SZA-M is supported by the Elite Journals Program at King Saud University through grant number PEJP-16-107. JM lab is supported by Columbia University COVID biobank and grant: UL1TR001873. Work in the Laboratory of Virology and Infectious Disease was supported by NIH grants P01AI138398-S1, 2U19AI111825, and R01AI091707-10S1, a George Mason University Fast Grant, and the G. Harold and Leila Y. Mathers Charitable Foundation. JLP is supported by a European Molecular Biology Organization Long-Term Fellowship (ALTF 380-2018). Work at the Neurometabolic Diseases Laboratory received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 824110 (EasiGenomics grant COVID-19/ PID12342) to A.P., and Roche and Illumina Covid Match Funds to M.G.. C.R.G and colleagues are supported by cInstituto de Salud Carlos III (COV20_01333 and COV20_01334), Spanish Ministry of Science and Innovation, with the funding of European Regional Development Fund-European Social Fund -FEDER-FSE; (RTC-2017-6471-1; AEI/FEDER, UE), and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas científicas del ITER para colaborar en la lucha contra la COVID-19”). D.C.V. is supported by the Fonds de la recherche en santé du Québec clinician-scientist scholar program. Helen Su is adjunct faculty at the University of Pennsylvania. A-L.N. was supported by the Foundation Bettencourt Schueller. The Amsterdam UMC Covid-19 Biobank was funded by the Netherlands Organization for Health Research and Development (ZonMw, NWO-vici 91819627), The Corona Research Fund (Amsterdam UMC), Dr. J. C. Vaillantfonds, and Amsterdam UMC. Work on COVID-19 at the AG-S lab is partly supported by NIH supplements to grants U19AI135972, U19AI142733 and R35 HL135834, and to contract HHSN272201800048C, by a DoD supplement to grant W81XWH-20-1-0270, by DARPA project HR0011-19-2-0020, by CRIP (Center for Research on Influenza Pathogenesis), a NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract HHSN272201400008C), by an NIAID funded Collaborative Influenza Vaccine Innovation Center (SEM-CIVIC, contract 75N93019C00051) and by the generous support of the JPB Foundation, the Open Philanthropy Project (research grant 2020-215611(5384)) and anonymous donors. The Virscan analysis presented in fig. S11 was performed with financial support from Sidra Medicine
Published: 2020

8. Association of VA Payment Reform for Dialysis with Spending, Access to Care, and Outcomes for Veterans with ESKD

Author: Amal N. Trivedi, Matthew L. Maciejewski, Shailender Swaminathan, Virginia Wang, Ann M. O’Hare, Vincent Mor, and Emily Corneau
Subjects: Male, medicine.medical_specialty, Epidemiology, media_common.quotation_subject, Dialysis care, Critical Care and Intensive Care Medicine, Ambulatory Care Facilities, 01 natural sciences, Health Services Accessibility, 03 medical and health sciences, 0302 clinical medicine, Renal Dialysis, Humans, Medicine, Limited capacity, 030212 general & internal medicine, 0101 mathematics, Dialysis facility, Veterans Affairs, health care economics and organizations, Reimbursement, Aged, Retrospective Studies, media_common, Transplantation, Payment reform, business.industry, 010102 general mathematics, Interrupted Time Series Analysis, Original Articles, Contract Services, Middle Aged, Payment, humanities, United States, Survival Rate, United States Department of Veterans Affairs, Nephrology, Family medicine, Insurance, Health, Reimbursement, Kidney Failure, Chronic, Female, Dialysis (biochemistry), business
Abstract: BACKGROUND AND OBJECTIVES: Because of the limited capacity of its own dialysis facilities, the Department of Veterans Affairs (VA) Veterans Health Administration routinely outsources dialysis care to community providers. Prior to 2011—when the VA implemented a process of standardizing payments and establishing national contracts for community-based dialysis care—payments to community providers were largely unregulated. This study examined the association of changes in the Department of Veterans Affairs payment policy for community dialysis with temporal trends in VA spending and veterans’ access to dialysis care and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: An interrupted time series design and VA, Medicare, and US Renal Data System data were used to identify veterans who received VA–financed dialysis in community-based dialysis facilities before (2006–2008), during (2009–2010), and after the enactment of VA policies to standardize dialysis payments (2011–2016). We used multivariable, differential trend/intercept shift regression models to examine trends in average reimbursement for community-based dialysis, access to quality care (veterans’ distance to community dialysis, number of community dialysis providers, and dialysis facility quality indicators), and 1-year mortality over this time period. RESULTS: Before payment reform, the unadjusted average per-treatment reimbursement for non–VA dialysis care varied widely ($47–$1575). After payment reform, there was a 44% reduction ($44–$250) in the adjusted price per dialysis session (P
Published: 2020

9. Evaluation of Bead-Based Assays for the Isolation of Foodborne Viruses from Low-Moisture Foods

Author: Nathalie Corneau, Angela Chen, Jennifer Harlow, Sabah Bidawid, and Neda Nasheri
Subjects: Food Handling, viruses, ved/biology.organism_classification_rank.species, Food Contamination, medicine.disease_cause, Microbiology, Virus, Bead (woodworking), 03 medical and health sciences, medicine, Animals, Humans, Food science, 030304 developmental biology, 0303 health sciences, Feline calicivirus, biology, Moisture, 030306 microbiology, ved/biology, Norovirus, Outbreak, biology.organism_classification, Isolation (microbiology), Viruses, Food Microbiology, Virus Inactivation, Hepatitis A virus, Food Science, Murine norovirus
Abstract: Foodborne viruses such as norovirus and hepatitis A virus (HAV) are highly transmissible, persistent in the environment, and resistant to many conventional inactivation methods. Foods can become contaminated with these viruses either at the source of harvest or during food handling and processing. Multiple lines of evidence suggest that foodborne viruses can survive desiccation and dry conditions. Several foodborne virus outbreaks have been linked to low-moisture foods (LMFs), indicating that these foods can be vehicles of virus transmission. However, the efficiencies of common virus extraction methodologies have not been examined with LMFs. We adapted the International Organization for Standardization (ISO) 15216-1:2017 method for virus recovery for use with chocolate, pistachios, and cornflakes. We also developed a magnetic bead assay for the recovery of HAV from LMFs and used the porcine gastric mucin-coated magnetic beads (PGM-MBs) to extract norovirus surrogates, feline calicivirus (FCV), and murine norovirus (MNV) from the same LMFs. The efficiency of virus recovery using the bead-based assay was then compared with that of the ISO 15216-1:2017 method. In chocolate and pistachios, the recovery rates with the PGM-MB method were 5.6- and 21.3-fold higher, respectively, for FCV and 1.65- and 18-fold higher, respectively, for MNV than those with the ISO 15216-1:2017 method. However, the PGM-MB method failed to recover MNV and FCV from cornflakes. The recovery rates for HAV in chocolate, pistachios, and corn flakes with the magnetic bead method were 11.5-, 3-, and 5.6-fold higher, respectively, than those with the ISO 15216-1:2017 method. Thus, depending upon the food matrix and the target virus, the bead-based assays can be used to efficiently and rapidly extract viruses from LMFs. HIGHLIGHTS
Published: 2020

10. Hematopoietic stem cell transplantation using single UM171-expanded cord blood: a single-arm, phase 1–2 safety and feasibility study

Author: Léa Bernard, Qi Li, Mégane Tanguay, Jalila Chagraoui, Bernhard Lehnertz, Jeroen J. A. van Kampen, Thomas Kiss, Frédéric Barabé, Séverine Landais, Jan J. Cornelissen, Jean Roy, Silvy Lachance, Fannie Larochelle, Sandra Cohen, Nadia M. Bambace, Anne Marinier, Jean-Sébastien Delisle, Pierre Caudrelier, Imran Ahmad, Maude Dumont-Lagacé, Guy Sauvageau, Peter W. Zandstra, Elisa Tomellini, Lambert Busque, Philippe Bouchard, Sophie Corneau, Sébastien Lemieux, Denis-Claude Roy, Virology, and Hematology
Subjects: Adult, Male, medicine.medical_specialty, Indoles, Cord, Adolescent, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Disease-Free Survival, Blood cell, Young Adult, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Cell Self Renewal, Adverse effect, Cells, Cultured, Febrile Neutropenia, Proportional Hazards Models, business.industry, Graft Survival, Hematopoietic Stem Cell Transplantation, Infant, Newborn, Hematology, Middle Aged, Hematopoietic Stem Cells, medicine.disease, Surgery, Haematopoiesis, Pyrimidines, Treatment Outcome, medicine.anatomical_structure, Hematologic Neoplasms, 030220 oncology & carcinogenesis, Cord blood, Feasibility Studies, Female, Cord Blood Stem Cell Transplantation, Stem cell, business, Febrile neutropenia, 030215 immunology
Abstract: Summary Background Benefits of cord blood transplantation include low rates of relapse and chronic graft-versus-host disease (GVHD). However, the use of cord blood is rapidly declining because of the high incidence of infections, severe acute GVHD, and transplant-related mortality. UM171, a haematopoietic stem cell self-renewal agonist, has been shown to expand cord blood stem cells and enhance multilineage blood cell reconstitution in mice. We aimed to investigate the safety and feasibility of single UM171-expanded cord blood transplantation in patients with haematological malignancies who do not have a suitable HLA-matched donor. Methods This single-arm, open-label, phase 1–2 safety and feasibility study was done at two hospitals in Canada. The study had two parts. In part 1, patients received two cord blood units (one expanded with UM171 and one unmanipulated cord blood) until UM171-expanded cord blood demonstrated engraftment. Once engraftment was documented we initiated part 2, reported here, in which patients received a single UM171-expanded cord blood unit with a dose de-escalation design to determine the minimal cord blood unit cell dose that achieved prompt engraftment. Eligible patients were aged 3–64 years, weighed 12 kg or more, had a haematological malignancy with an indication for allogeneic hematopoietic stem cell transplant and did not have a suitable HLA-matched donor, and a had a Karnofsky performance status score of 70% or more. Five clinical sites were planned to participate in the study; however, only two study sites opened, both of which only treated adult patients, thus no paediatric patients (aged ClinicalTrials.gov , NCT02668315 . Findings Between Feb 17, 2016, and Nov 11, 2018, we enrolled 27 patients, four of whom received two cord blood units for safety purposes in part 1 of the study. 23 patients were subsequently enrolled in part 2 to receive a single UM171-expanded cord blood transplant and 22 patients received a single UM171-expanded cord blood transplantation. At data cutoff (Dec 31, 2018), median follow-up was 18 months (IQR 12–22). The minimal cord blood unit cell dose at thaw that achieved prompt engraftment as a single cord transplant after UM171 expansion was 0·52 × 105 CD34-positive cells. We successfully expanded 26 (96%) of 27 cord blood units with UM171. Among the 22 patients who received single UM171-expanded cord blood transplantation, median time to engraftment of 100 neutrophils per μL was 9·5 days (IQR 8–12), median time to engraftment of 500 neutrophils per μL was 18 days (12·5–20·0), and no graft failure occurred. Median time to platelet recovery was 42 days (IQR 35–47). The most common non-haematological adverse events were grade 3 febrile neutropenia (16 [73%] of 22 patients) and bacteraemia (nine [41%]). No unexpected adverse events were observed. One (5%) of 22 patients died due to treatment-related diffuse alveolar haemorrhage. Interpretation Our preliminary findings suggest that UM171 cord blood stem cell expansion is feasible, safe, and allows for the use of small single cords without compromising engraftment. UM171-expanded cord blood might have the potential to overcome the disadvantages of other cord blood transplants while maintaining the benefits of low risk of chronic GVHD and relapse, and warrants further investigation in randomised trials. Funding Canadian Institutes of Health Research, Canadian Cancer Society and Stem Cell Network.
Published: 2020

11. Two New Neutrophil Subsets Define a Discriminating Sepsis Signature

Author: Borok, Matthew, Didier, Nathalie, Gattazzo, Francesca, Ozturk, Teoman, Corneau, Aurélien, Rouard, Helene, Relaix, Frederic, Meghraoui-Kheddar, Aïda, Chousterman, Benjamin, Guillou, Noëlline, Barone, Sierra, Granjeaud, Samuel, Vallet, Helene, Guessous, Karim, de Roquetaillade, Charles, Boissonnas, Alexandre, Irish, Jonathan, Combadière, Christophe, Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU), Service d'Unité de gériatrie aigüe [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département d’Anesthésie-Réanimation-SMUR [Hôpital Lariboisière], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), BRUNEL, Nadège, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: PD-L1, Pulmonary and Respiratory Medicine, medicine.medical_specialty, diagnosis, Neutrophils, [SDV]Life Sciences [q-bio], Interleukin-3 Receptor alpha Subunit, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Sensitivity and Specificity, Severity of Illness Index, B7-H1 Antigen, Diagnosis, Differential, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Clinical Decision Rules, Intensive care, medicine, Humans, Longitudinal Studies, Clinical care, Intensive care medicine, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, Cause of death, 0303 health sciences, biology, business.industry, Receptors, IgG, Flow Cytometry, medicine.disease, CD123, Case-Control Studies, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Linear Models, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Interleukin-3 receptor, business, Biomarkers
Abstract: International audience; Background: Skeletal muscle is one of the only mammalian tissues capable of rapid and efficient regeneration after trauma or in pathological conditions. Skeletal muscle regeneration is driven by the muscle satellite cells, the stem cell population in interaction with their niche. Upon injury, muscle fibers undergo necrosis and muscle stem cells activate, proliferate and fuse to form new myofibers. In addition to myogenic cell populations, interaction with other cell types such as inflammatory cells, mesenchymal (fibroadipogenic progenitors—FAPs, pericytes) and vascular (endothelial) lineages are important for efficient muscle repair. While the role of the distinct populations involved in skeletal muscle regeneration is well characterized, the quantitative changes in the muscle stem cell and niche during the regeneration process remain poorly characterized. Methods: We have used mass cytometry to follow the main muscle cell types (muscle stem cells, vascular, mesenchymal and immune cell lineages) during early activation and over the course of muscle regeneration at D0, D2, D5 and D7 compared with uninjured muscles. Results: Early activation induces a number of rapid changes in the proteome of multiple cell types. Following the induction of damage, we observe a drastic loss of myogenic, vascular and mesenchymal cell lineages while immune cells invade the damaged tissue to clear debris and promote muscle repair. Immune cells constitute up to 80% of the mononuclear cells 5 days post-injury. We show that muscle stem cells are quickly activated in order to form new myofibers and reconstitute the quiescent muscle stem cell pool. In addition, our study provides a quantitative analysis of the various myogenic populations during muscle repair. Conclusions: We have developed a mass cytometry panel to investigate the dynamic nature of muscle regeneration at a single-cell level. Using our panel, we have identified early changes in the proteome of stressed satellite and niche cells. We have also quantified changes in the major cell types of skeletal muscle during regeneration and analyzed myogenic transcription factor expression in satellite cells throughout this process. Our results highlight the progressive dynamic shifts in cell populations and the distinct states of muscle stem cells adopted during skeletal muscle regeneration. Our findings give a deeper understanding of the cellular and molecular aspects of muscle regeneration.
Published: 2022

12. Decisão compartilhada na atenção primária e desfechos em saúde: uma revisão integrativa

Author: Gabriel Glebocki and Felipe Gonçalves Corneau
Subjects: medicine.medical_specialty, Medicine (General), Avaliação de Resultados da Assistência ao Paciente, Theoretical definition, Avaliação de Processos e Resultados em Cuidados de Saúde, General Medicine, Outcome (game theory), Atenção primária à saúde, chemistry.chemical_compound, Quality research, One Health, R5-920, chemistry, Family medicine, medicine, Tomada de Decisão Clínica, Glycated hemoglobin, Risks and benefits, Public aspects of medicine, RA1-1270, Psychology, Association (psychology), Depression (differential diagnoses)
Abstract: O processo de decisão compartilhada pode ser definido a partir dos seguintes elementos: 1. há, no mínimo, duas pessoas envolvidas no processo de decisão, o médico e o paciente; 2. médico e paciente compartilham informações; 3. ambos contribuem para o processo decisório expondo suas preferências; 4. chega-se a uma decisão sobre a qual todos os envolvidos concordam. Seu emprego se justifica principalmente pelo aspecto ético de incluir o paciente nas decisões cujas consequências ele sofrerá. Todavia, muito se questiona sobre a relação desta prática com os desfechos em saúde. Objetivos: Esse estudo tem por objetivo avaliar a relação entre a prática da decisão compartilhada e desfechos em saúde em cenários de atenção primária à saúde. Métodos: Realizou-se uma revisão integrativa da literatura e foram incluídos artigos que tivessem medidas empíricas de decisão compartilhada durante o encontro clínico, cujo cenário fosse a atenção primária à saúde e que apresentasse avaliação de, pelo menos, um desfecho em saúde. Resultados: Inclui-se dez artigos no estudo, e os temas abordados são depressão (4 artigos), hipertensão (2), diabetes (1), risco cardiovascular (1), rastreio de câncer colorretal (1) e infertilidade (1). Metade dos estudos sobre depressão encontraram associação positiva entre a decisão compartilhada e a melhora dos sintomas depressivos. Dos estudos sobre hipertensão, não se encontrou associações estatisticamente significativas. Do estudo sobre diabetes, não se constatou correlação positiva entre decisão compartilhada e redução da hemoglobina glicada e do LDL. Compartilhar a decisão ao discutir risco cardiovascular não piorou o escore deste indicador 6 meses após a consulta. Com relação ao rastreio de câncer colorretal, discutir riscos e benefícios e avaliar as preferências dos pacientes se associou negativamente à realização dos testes de rastreio. Por fim, decisão compartilhada se associou a melhor experiência de cuidado para pessoas em acompanhamento para infertilidade na atenção primária. Dois estudos cronometraram consultas e não se observou diferenças de tempo entre aqueles que usaram e os que não usaram a decisão compartilhada. Quatro estudos não definiram conceitualmente a decisão compartilhada e quatro estudos não utilizaram ferramentas validadas para medi-la. Conclusão: Com relação aos desfechos avaliados, os artigos incluídos nesta revisão apresentam resultados ambíguos, com aparente tendência de correlação positiva entre decisão compartilhada e desfechos. Todavia, a falta de uniformidade com relação à definição conceitual de decisão compartilhada parece ser potencial barreira para pesquisas de maior qualidade na área.
Published: 2021

13. Antipsychotic initiation and new diagnoses excluded from quality-measure reporting among Veterans in community nursing homes contracted by the Veterans Health Administration in the United States

Author: Amy L Mochel, Emily Corneau, Kate H Magid, Cari Levy, Vincent Mor, Portia Y. Cornell, and Patience Moyo
Subjects: medicine.medical_specialty, Minimum Data Set, business.industry, medicine.medical_treatment, Veterans Health, Disease, medicine.disease, Logistic regression, Medicare, United States, Nursing Homes, Psychiatry and Mental health, Schizophrenia, medicine, Humans, Dementia, Medical diagnosis, Medical prescription, Psychiatry, Antipsychotic, business, Community nursing, Aged, Antipsychotic Agents, Veterans
Abstract: Objectives To assess whether prevailing antipsychotic use rates in community nursing homes (CNH) influence new initiation of antipsychotics and diagnosis with antipsychotic indications among Veterans. Methods We used linked 2013-2016 Veterans Administration (VA) data, Medicare claims, Nursing Home Compare, and Minimum Data Set (MDS) assessments. The exposure was the proportion (in quintiles) of all CNH residents prescribed antipsychotics in the quarter preceding a Veteran's admission date. Using adjusted logistic regression, we analyzed two outcomes measured using MDS: antipsychotic initiation, and new diagnosis of an antipsychotic quality-measure exclusionary condition (i.e., schizophrenia, Tourette's syndrome, or Huntington's disease). Results Among 8201 Veterans without an indication for antipsychotics at baseline, 21.1% initiated antipsychotics and 3.5% were newly diagnosed with any exclusionary diagnosis after CNH admission. Schizophrenia accounted for almost all (96.8%) the new diagnoses. Antipsychotic initiation increased with higher CNH antipsychotic use rates: OR = 2.55, 95% CI: 2.08--3.12, quintile 5 versus 1. CNHs with the highest prevalent use of antipsychotics were associated with increased odds of Veterans acquiring an exclusionary diagnosis (OR = 2.09, 95% CI: 1.32-3.32, quintile 5 vs. 1). Conclusions Incident antipsychotic use is common among Veterans admitted to CNHs. CNH antipsychotic prescribing practices are associated with Veterans being newly diagnosed with antipsychotic prescription indications, primarily schizophrenia.
Published: 2021

14. A monocyte/dendritic cell molecular signature of SARS-CoV-2-related multisystem inflammatory syndrome in children with severe myocarditis

Author: Cécile Masson, Aurélien Corneau, Florence Moulin, Ghaith Abdessalem, Pedro Gonçalves, Marianne Leruez, James P. Di Santo, Mathie Lorrot, Julie Toubiana, Julien Haroche, Camille Bruneau, Isabelle Melki, Bruno Charbit, Zahra Belhadjer, Loïc de Pontual, Camille de Cevins, Brigitte Bader Meunier, Alain Fischer, Victor Garcia-Paredes, Brieuc P. Perot, Marine Luka, Damien Bonnet, Quentin Riller, Nikaïa Smith, Slimane Allali, Sonia Meynier, Aude Magérus, Christele Gras Leguen, Shen-Ying Zhang, Olivier Schwartz, Jean-Laurent Casanova, Frédéric Rieux-Laucat, Nicolas Cagnard, Francesco Carbone, Tinhinane Fali, Mélanie Parisot, Mickaël M. Ménager, Maxime Beretta, Mohammed Zarhrate, Christine Bole-Feysot, Vithura Pirabarakan, Ludivine Grzelak, Mehdi Oualha, Darragh Duffy, Laura Barnabei, Hugo Mouquet, Maxime Batignes, Alexandre Boullé, Boris Sorin, Marie-Claude Stolzenberg, Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Sanofi Aventis R&D [Chilly-Mazarin], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Rockefeller University [New York], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital universitaire Robert-Debré [Paris], Université Paris Cité (UPCité), CHU Trousseau [APHP], Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Jean Verdier [AP-HP], Université Paris 13 (UP13), Collège de France (CdF (institution)), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), and Université Paris Cité (UPC)
Subjects: Adult, Vascular Endothelial Growth Factor A, Chemokine, Myocarditis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MIS-C, Monocytes, chemistry.chemical_compound, Viewpoint, scRNA-seq, medicine, otorhinolaryngologic diseases, Humans, Kawasaki Disease, Child, Connective Tissue Diseases, biology, business.industry, SARS-CoV-2, Monocyte, NF-kappa B, COVID-19, General Medicine, Dendritic Cells, Gene signature, medicine.disease, Pathophysiology, Systemic Inflammatory Response Syndrome, Vascular endothelial growth factor, medicine.anatomical_structure, Cytokine, chemistry, TNF-α and NF-κB signaling, Immunology, biology.protein, Cytokines, Tumor necrosis factor alpha, lack of responses to type I and type II IFN secretion, Clinical and Translational Article, Chemokines, myocarditis, business, PIMS-TS
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. Methods To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. Findings The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. Conclusions These results provide potential for a better understanding of disease pathophysiology. Funding Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d’Excellence ‘‘Milieu Intérieur,” grant ANR-10-LABX-69-01; ANR-flash Covid19 “AIROCovid” and “CoVarImm”), Institut National de la Santé et de la Recherche Médicale (INSERM), and the “URGENCE COVID-19” fundraising campaign of Institut Pasteur., Graphical abstract, Context and significance Children with SARS-CoV-2 infection were initially thought to have only mild COVID-19 symptoms. However, several weeks into the first wave of SARS-CoV-2 infections, there was a surge of a postacute pathology called multisystem inflammatory syndrome in children (MIS-C). The authors recruited a cohort of children with suspicion of SARS-CoV-2 infection and uncovered hyperinflammation, hypoxic conditions, exacerbation of TNF-α signaling via NF-κB, and absence of responses to type I and type II IFN secretion in the most severe forms of MIS-C with severe myocarditis. This work led the authors to identify in monocytes and validate in peripheral blood mononuclear cells a molecular signature of 25 genes that allows discrimination of the most severe forms of MIS-C with myocarditis., Multiparametric analysis identifies, in monocytes and dendritic cells, a molecular signature of the most severe forms of multisystem inflammatory syndrome in children caused by SARS-CoV-2 infection. Severe myocarditis is characterized by an excess of TNF-α signaling via NF-κB, hypoxic conditions, and hyperinflammation in the absence of type I and type II interferon responses.
Published: 2021

15. Implementation of A Psychiatric Consultation for Healthcare Workers During First Wave of COVID-19 Outbreak: A Qualitative and Quantitative Analysis

Author: Gérard Langlois, Guido Bondolfi, Diana Apetrei, Chiara Chiabotto, Alexandra Groz, Bruno Corneau, Verena Marini, and Lamyae Benzakour
Subjects: medicine.medical_specialty, Quantitative analysis (finance), Coronavirus disease 2019 (COVID-19), Psychiatric consultation, business.industry, Family medicine, Health care, Medicine, Outbreak, business
Abstract: Background:Prevention and management strategies of mental suffering in healthcare workers appeared as important challenges during COVID-19 pandemic. This article aims to 1) Identify potential psychiatric disorders for healthcare workers during the first wave of the COVID-19 outbreak; 2) Describe the implementation of a psychiatric consultation for healthcare workers; 3) Present the activity report of this consultation; 4) Analyze and learn from this experience.Methods: The authors identified specific risks for healthcare workers mental health to be anxiety, depression, burnout and traumatic symptoms. The authors performed a retrospective quantitative analysis of socio-demographic and clinical data, in addition to psychiatric scales scores for the main potential psychiatric risks (PDI, PDEQ, PCL-5, HADS, MBI-HSS) and post-hoc qualitative analysis of written interviews. Means and frequencies were calculated for all the variables collected. Results: 25 healthcare workers were consulted between 19 th March 2020 and 12 th June 2020, 18 who accepted to participate to the study. Authors found 78.57% presented high peritraumatic dissociation, 78.57%, high peritraumatic distress, 68.75%, severe anxiety symptoms, and 31.25%, severe depression symptoms. Concerning burnout, authors found 35.29% had a moderate,and 23.53% a high level of Emotional Exhaustion; 17.65%, a moderate, and 23.53%, a high level of Depersonalization; 11.76%, a low, and 35.29%, a moderate level of Personal Achievement. In the qualitative analysis of the written interview, authors found a direct link with COVID-19, primarily concerning traumatic stressors, and secondarily with work-related stress. Conclusions: This study confirms the psychiatric consequences during the first wave of the COVID-19 epidemic for healthcare workers. These results suggest that for healthcare workers, early detection of traumatic reactions, valorization of individual effort, and limitations on work overload, are potential key preventative measures.
Published: 2021

16. NK Cell Responses in Zika Virus Infection Are Biased towards Cytokine-Mediated Effector Functions

Author: Hans Yssel, Aurélien Corneau, Luana Leandro Gois, Christopher Maucourant, Catherine Blanc, Maria Fernanda Rios Grassi, Nadine Tarantino, Aïda Meghraoui-Kheddar, Vincent Vieillard, Assia Samri, Antonio Bandeira, Gabriel Andrade Nonato Queiroz, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, Cell, Lymphocyte Activation, Zika virus, Cohort Studies, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Immune system, Pregnancy, MHC class I, STAT5 Transcription Factor, medicine, Humans, Immunology and Allergy, Mass cytometry, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, biology, Tumor Necrosis Factor-alpha, Zika Virus Infection, Receptors, KIR3DL1, Zika Virus, biology.organism_classification, Interleukin-12, 3. Good health, Killer Cells, Natural, Flavivirus, Cytokine, medicine.anatomical_structure, Acute Disease, biology.protein, Female, KIR3DL1, 030215 immunology
Abstract: Zika virus (ZIKV) is a mosquito-borne flavivirus that has emerged as a global concern because of its impact on human health. ZIKV infection during pregnancy can cause microcephaly and other severe brain defects in the developing fetus and there have been reports of the occurrence of Guillain-Barré syndrome in areas affected by ZIKV. NK cells are activated during acute viral infections and their activity contributes to a first line of defense because of their ability to rapidly recognize and kill virus-infected cells. To provide insight into NK cell function during ZIKV infection, we have profiled, using mass cytometry, the NK cell receptor-ligand repertoire in a cohort of acute ZIKV-infected female patients. Freshly isolated NK cells from these patients contained distinct, activated, and terminally differentiated, subsets expressing higher levels of CD57, NKG2C, and KIR3DL1 as compared with those from healthy donors. Moreover, KIR3DL1+ NK cells from these patients produced high levels of IFN-γ and TNF-α, in the absence of direct cytotoxicity, in response to in vitro stimulation with autologous, ZIKV-infected, monocyte-derived dendritic cells. In ZIKV-infected patients, overproduction of IFN-γ correlated with STAT-5 activation (r = 0.6643; p = 0.0085) and was mediated following the recognition of MHC class 1–related chain A and chain B molecules expressed by ZIKV-infected monocyte-derived dendritic cells, in synergy with IL-12 production by the latter cells. Together, these findings suggest that NK cells contribute to the generation of an efficacious adaptive anti-ZIKV immune response that could potentially affect the outcome of the disease and/or the development of persistent symptoms.
Published: 2021

17. Immune checkpoint inhibitors increase T cell immunity during SARS-CoV-2 infection

Author: Jeremy Boussier, Olivier Peyrony, Majdi Jebali, Bruno Charbit, Benjamin Terrier, Nora Kramkimel, Céleste Lebbé, Aurélien Corneau, Magnus Fontes, Jérôme LeGoff, Selim Aractingi, Laetitia Da Meda, Frédéric Rieux-Laucat, Vincent Calmettes, P. Tetu, Olivier Schwartz, Laura Barnabei, Darragh Duffy, Nikaïa Smith, Clara Allayous, Jérôme Hadjadj, Timothée Bruel, Charles Cassius, Nader Yatim, Isabelle Staropoli, F. Herms, Catherine Blanc, Ludivine Grzelak, Barouyr Baroudjian, Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris]-Université Paris Cité (UPCité), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Laboratoire Roche [Boulogne-Billancourt], Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), N.Y. and C.L. acknowledge grant from the ARC Flash Covid-19 and Cancer call (ONCOVID). N.Y. and D.D. acknowledge grants from the Institut Pasteur for Covid-19 research and the ANR Flash Covid-19 call (CoVarImm). N.S. was supported by an Institut Pasteur Roux Cantarini fellowship. B.T. was supported by the Fonds IMMUNOV, for Innovation in Immunopathology. F.R.-L. acknowledges grants from the ANR Flash Covid-19 (AIROCOVID) and the FAST foundation. The study was also supported by the Institut National de la Santé et de la Recherche Médicale (Inserm) and by government grants managed by the Agence Nationale de la Recherche as part of the 'Investment for the future' program (ANR-10 IAHU-01 and ANR-18-RHUS-0010). L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the future' program., ANR-20-COVI-0053,CoVarImm,Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence(2020), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vougny, Marie-Christine, Variation de la réponse immune systémique et muqueuse pendant l'infection par le SRAS-CoV-2 et la convalescence - - CoVarImm2020 - ANR-20-COVI-0053 - COVID-19 - VALID, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation - - ATRACTION2018 - ANR-18-RHUS-0010 - RHUS - VALID, Génétique et Epigénétique Nouvelle Ecole - - GENE2017 - ANR-17-EURE-0013 - EURE - VALID, Université de Paris - - Université de Paris2018 - ANR-18-IDEX-0001 - IDEX - VALID, Virus et Immunité - Virus and immunity (CNRS-UMR3569), Vaccine Research Institute [Créteil, France] (VRI), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Paris (UP)
Subjects: Male, animal diseases, T-Lymphocytes, Adaptive Immunity, CD8-Positive T-Lymphocytes, Antibodies, Viral, Lymphocyte Activation, 0302 clinical medicine, Interferon, Prospective Studies, Immune Checkpoint Inhibitors, Melanoma, Research Articles, 0303 health sciences, Multidisciplinary, Effector, SciAdv r-articles, Middle Aged, Acquired immune system, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Spike Glycoprotein, Coronavirus, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, medicine.drug, Research Article, [SDV.IMM] Life Sciences [q-bio]/Immunology, T cell, Immunology, Inflammation, chemical and pharmacologic phenomena, 03 medical and health sciences, Immune system, medicine, Humans, Health and Medicine, 030304 developmental biology, Aged, business.industry, SARS-CoV-2, COVID-19, biochemical phenomena, metabolism, and nutrition, medicine.disease, Coronavirus, bacteria, business, Immunologic Memory, CD8
Abstract: Immune checkpoint inhibitors for melanoma improve adaptive T cell immunity during COVID-19 without exacerbating inflammation., The COVID-19 pandemic has spread worldwide, yet the role of antiviral T cell immunity during infection and the contribution of immune checkpoints remain unclear. By prospectively following a cohort of 292 patients with melanoma, half of which treated with immune checkpoint inhibitors (ICIs), we identified 15 patients with acute or convalescent COVID-19 and investigated their transcriptomic, proteomic, and cellular profiles. We found that ICI treatment was not associated with severe COVID-19 and did not alter the induction of inflammatory and type I interferon responses. In-depth phenotyping demonstrated expansion of CD8 effector memory T cells, enhanced T cell activation, and impaired plasmablast induction in ICI-treated COVID-19 patients. The evaluation of specific adaptive immunity in convalescent patients showed higher spike (S), nucleoprotein (N), and membrane (M) antigen-specific T cell responses and similar induction of spike-specific antibody responses. Our findings provide evidence that ICI during COVID-19 enhanced T cell immunity without exacerbating inflammation.
Published: 2021

18. Differences between men and women in dietary intakes and metabolic profile in response to a 12-week nutritional intervention promoting the Mediterranean diet

Author: Vicky Leblanc, Anne-Marie Hudon, Marie-Michelle Royer, Louise Corneau, Sylvie Dodin, Catherine Bégin, and Simone Lemieux
Subjects: Differences between men and women, Mediterranean diet, Cardiovascular risk, Self-determination theory, Nutrition. Foods and food supply, TX341-641, Medicine
Abstract: Few studies have compared men and women in response to nutritional interventions but none has assessed differences between men and women in the response to a nutritional intervention programme based on the self-determination theory (SDT) and using the Mediterranean diet (MedDiet) as a model of healthy eating, in a context of CVD prevention and within a non-Mediterranean population. The present study aimed to document differences between men and women in changes in dietary, anthropometric and metabolic variables, in response to a nutritional intervention programme promoting the adoption of the MedDiet and based on the SDT. A total of sixty-four men and fifty-nine premenopausal women presenting risk factors for CVD were recruited through different media advertisements in the Québec City Metropolitan area (Canada). The 12-week nutritional programme used a motivational interviewing approach and included individual and group sessions. A validated FFQ was administered to evaluate dietary intakes from which a Mediterranean score (Medscore) was derived. Both men and women significantly increased their Medscore in response to the intervention (P
Published: 2015
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19. A monocyte/dendritic cell molecular signature of SARS-CoV2-related multisystem inflammatory syndrome in children (MIS-C) with severe myocarditis

Author: Ludivine Grzelak, Maxime Beretta, Slimane Allali, Aude Magérus, Hugo Mouquet, Maxime Batignes, Isabelle Melki, Olivier Schwartz, Quentin Riller, Mehdi Oualha, Nicolas Cagnard, Christine Bole-Feysot, Camille de Cevins, James P. Di Santo, Christele Gras Leguen, Florence Moulin, Jean-Laurent Casanova, Cécile Masson, Aurélien Corneau, Damien Bonnet, Vithura Pirabarakan, Mickaël M. Ménager, Camille Bruneau, Brieuc P. Perot, Francesco Carbone, Darragh Duffy, Mohammed Zarhrate, Marie-Claude Stolzenberg, Alexandre Boullé, Mélanie Parisot, Boris Sorin, Ghaith Abdessalem, Alain Fischer, Marianne Leruez, Julie Toubiana, Victor Garcia-Paredes, Mathie Lorrot, Loïc de Pontual, Zahra Belhadjer, Bruno Charbit, Tinhinane Fali, Marine Luka, Nikaïa Smith, Brigitte Bader Meunier, Shen-Ying Zhang, Sonia Meynier, Fredéric Rieux Laucat, Julien Haroche, Pedro Gonçalves, Laura Barnabei, Inflammatory Responses and Transcriptomic Networks in diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sanofi Aventis R&D [Chilly-Mazarin], Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris], Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Immunité Innée - Innate Immunity, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163), Rockefeller University [New York], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP Hôpital universitaire Robert-Debré [Paris], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département des urgences pédiatriques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Virologie [CHU Necker], Département de Pédiatrie et maladies infectieuses [CHU Necker], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie [Jean Verdier], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Collège de France (CdF (institution)), Biodiversité et Epidémiologie des Bactéries pathogènes - Biodiversity and Epidemiology of Bacterial Pathogens, The study was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), by the 'URGENCE COVID-19' fundraising campaign of Institut Pasteur, by the Atip-Avenir, Emergence ville de Paris program and fond de dotation Janssen Horizon and by government grants managed by the Agence National de la Recherche as part of the 'Investment for the Future' program (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010, Laboratoire d’Excellence ‘‘Milieu Intérieur', grant ANR-10-LABX-69-01), the Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL and 'CoVarImm' to DD and JDS), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). The LabTech Single Cell@Imagine is supported by the Paris Region and the 'Investissements d’avenir' program through the 2019 ATF funding – Sésame Filières PIA (Grant N°3877871). CdC is the recipient of a CIFRE-PhD (Sanofi). L.B. was a recipient of an Imagine institute PhD international program supported by the Fondation Bettencourt Schueller. L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the Future' program. S.M. was a recipient of an INSERM and Institut Imagine post-doctorat program supported by the Fondation pour la Recherche Médicale (FRM N°SPF20170938825). NS was a recipient of the Pasteur-Roux-Cantarini Fellowship. VGP obtained an Imagine international PhD fellowship program supported by the Fondation Bettencourt Schueller. BPP is the recipient of an ANRS post-doctoral fellowship., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), ANR-20-COVI-0022,AIROCovid19,Analyse Omics de la réponse immune aigue au cours de l'infection à Covid19: rationnel moléculaire pour un traitement ciblé(2020), ANR-17-EURE-0013,GENE,Génétique et Epigénétique Nouvelle Ecole(2017), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: 0303 health sciences, Chemokine, Myocarditis, biology, business.industry, Monocyte, Dendritic cell, Gene signature, medicine.disease_cause, medicine.disease, Pathophysiology, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Immunology, biology.protein, medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, business, Oxidative stress, 030304 developmental biology
Abstract: SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κB activity, TNF-α signaling, associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.
Published: 2021

20. Mass Cytometry: a robust platform for the comprehensive immunomonitoring of CAR‐T‐cell therapies

Author: Damien Roos-Weil, Elena Litvinova, Amélie Guihot, Christophe Parizot, Françoise Norol, Catherine Blanc, Eve Todesco, Mustapha Cherai, Stéphanie Nguyen, Aurélien Corneau, Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SPI.OTHER]Engineering Sciences [physics]/Other, 0303 health sciences, Receptors, Chimeric Antigen, business.industry, T-Lymphocytes, [SDV]Life Sciences [q-bio], Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Flow Cytometry, Immunotherapy, Adoptive, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Antigens, CD, 030220 oncology & carcinogenesis, Cancer research, Medicine, Humans, Mass cytometry, Cytophotometry, Lymphoma, Large B-Cell, Diffuse, Car t cells, business, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: International audience
Published: 2021

21. Impact des inhibiteurs de checkpoints immunitaires au cours de la COVID-19 chez les patients atteints de mélanome

Author: Aurélien Corneau, Selim Aractingi, Ludivine Grzelak, Timothée Bruel, P. Tetu, Jérôme Hadjadj, Catherine Blanc, Nikaïa Smith, L. Da Meda, C. Lebbé, Benjamin Terrier, J. Le Goff, Olivier Schwartz, Clara Allayous, J. Boussier, Nader Yatim, Isabelle Staropoli, Frédéric Rieux-Laucat, Darragh Duffy, and Nora Kramkimel
Subjects: Gynecology, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Co018, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Gastroenterology, Internal Medicine, medicine, business
Abstract: Introduction La restauration immunitaire induite par les inhibiteurs de checkpoints immunitaires ont révolutionné le pronostic des cancers métastatiques [1]. La contribution de cette stratégie thérapeutique pour la prise en charge des infections reste toutefois controversée, malgré quelques études en faveur de leur utilisation, notamment dans le contexte de paralysie immunitaire au décours d’un sepsis sévère [2], [3], ou dans les situations d’épuisement immunitaire au cours des infections virales chroniques [4], [5]. Au cours de la COVID-19, des études suggèrent qu’un état d’épuisement immunitaire en lien avec une anergie et/ou une déplétion des lymphocytes T serait partiellement responsable de la virulence du SARS-CoV-2 [6], [7], [8], [9], [10]. Certains proposent donc l’utilisation des anti-PD1 comme stratégie thérapeutique tandis que d’autres suggèrent qu’au contraire, elle pourrait aggraver l’hyperinflammation [11], [12]. Patients et méthodes Nous avons suivi de façon prospective 292 patients atteints de mélanome lors de la première vague de COVID-19 (de mars à juin 2020) dont la moitié était traitée par immunothérapie (anti-PD1 ± anti-CTLA4). Les patients présentant des symptômes de COVID-19 étaient dépistés par PCR. Une sérologie SARS-CoV-2 était recherchée de façon systématique. Les patients présentant une infection symptomatique active ( 21 jours du début des symptômes, PCR négative, sérologie positive) ont été inclus pour une étude approfondie de la réponse immunitaire par une analyse transcriptionnelle (Nanostring), protéomique (SIMOA, Luminex) et cellulaire (cytométrie de masse). Résultats Quinze patients atteints de COVID-19 ont été identifiés (infection active ou convalescente) avec une estimation de la séroprévalence à 8,6 % de la cohorte. Quatre patients sur 15 ont nécessité une hospitalisation (26,7 %). Les données cliniques ne retrouvaient pas d’éléments en faveur d’une forme plus sévère de COVID-19 lors d’un traitement par anti-PD1, seul un patient ayant également une leucémie lymphoïde chronique, a développé une forme sévère de la COVID-19 et est décédé de défaillance respiratoire. L’analyse de la réponse immunitaire, en comparaison avec une cohorte de patients non traités par immunothérapie, retrouvait une réponse immunitaire innée semblable dans les deux cohortes. De même, le taux d’anticorps anti-Spike (IgG et IgA), la capacité neutralisante ainsi que la longévité des anticorps (suivi du taux sur une période d’1 an) étaient similaires en présence ou non d’un traitement par immunothérapie. En revanche, l’analyse de la réponse cellulaire mettait en évidence, chez les patients traités par immunothérapie, une expansion de la population de lymphocytes T CD8+ effecteurs mémoires, une augmentation de l’activation des lymphocytes T CD4+ et CD8+, et une augmentation la production d’IFN-gamma lors d’une stimulation ex-vivo par des peptides issus du SARS-CoV-2. Conclusion Nos résultats sont en faveur d’une augmentation de la réponse cellulaire T anti-SARS-CoV-2 lors d’un traitement par anti-PD1 chez les patients suivis pour mélanome, et de l’absence d’une exacerbation de la réponse inflammatoire. Il est nécessaire de confirmer ces résultats avec un plus grand nombre de patients, dans d’autres types de cancers et dans d’autres centres.
Published: 2021

22. Poor Adherence to Dietary Guidelines Among French-Speaking Adults in the Province of Quebec, Canada: The PREDISE Study

Author: Véronique Provencher, Didier Brassard, Mathieu Bélanger, Benoît Lamarche, Julie Robitaille, Marie-Claude Vohl, Louise Corneau, Catherine Laramée, Luigi Bouchard, Simone Lemieux, Sophie Desroches, Catherine Bégin, Rémi Rabasa-Lhoret, Charles Couillard, Marie-France Langlois, and Julie Houle
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Cross-sectional study, Population, 030204 cardiovascular system & hematology, Diet Surveys, Body Mass Index, Nutrition Policy, Young Adult, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Interquartile range, Environmental health, medicine, Humans, Mass index, 030212 general & internal medicine, education, Aged, 2. Zero hunger, education.field_of_study, business.industry, Public health, Quebec, Feeding Behavior, Middle Aged, Confidence interval, 3. Good health, Cross-Sectional Studies, Income, Educational Status, Female, Median body, Self Report, Cardiology and Cardiovascular Medicine, business, Body mass index
Abstract: Background Regular monitoring of the population's food and nutrient intake is essential to develop effective nutrition-focused public health policies. The aim of this study was to provide dietary intake estimates using an age- and sex-representative sample of French-speaking adults with Internet access from 5 administrative regions in the province of Quebec, Canada. Methods PREDicteurs Individuels, Sociaux et Environnementaux (PREDISE) is a multicentre cross-sectional study that used a Web-based approach to collect individual, social, and environmental data on factors associated with adherence to dietary recommendations. Dietary intake was estimated from the average of 3 validated Web-based 24-hour recalls. Results Mean (± SD) age of the 1147 participants (50.2% women) was 43.2 ± 4.6 years and median body mass index was 26.3 (interquartile range, 23.3-30.3). Less than 25% of participants met Canada's Food Guide recommendations for vegetables and fruit intake (prevalence, 23.6%; 95% confidence interval [CI], 21.1-26.0). Most participants reported consuming more than 2300 mg of sodium (prevalence, 80.5%; 95% CI, 78.2-82.7) and more than 10% energy as saturated fats (prevalence, 74.2%; 95% CI, 71.6-76.7). Mean Canadian Healthy Eating Index score on a scale of 0-100 was 54.5 (95% CI, 53.8-55.2), reflecting relatively poor diet quality according to current dietary recommendations. Conclusions Self-reported dietary intakes measured using a new validated Web-based 24-hour recall in this sample of French-speaking adults from Quebec and with access to Internet suggest low adherence to current Canadian dietary guidelines. These data emphasize the need for more effective nutrition-focused public health policies to maximize cardiovascular disease prevention at the population level.
Published: 2018

23. Inequities in access to VA'S aid and attendance enhanced pension benefit to help Veterans pay for long-term care

Author: Emily Corneau, Courtney Harold Van Houtven, David C. Aron, Susan M. Allen, Kali S. Thomas, Portia Y. Cornell, and David Dosa
Subjects: Gerontology, Health Status, Veterans Health, Medicare, 03 medical and health sciences, Pensions, 0302 clinical medicine, Sex Factors, Medicine, Humans, 030212 general & internal medicine, health care economics and organizations, Veterans, Receipt, Pension, business.industry, 030503 health policy & services, Health Policy, Attendance, Age Factors, Secondary data, Health Services, Patient Acceptance of Health Care, Long-Term Care, United States, Outreach, Long-term care, United States Department of Veterans Affairs, Socioeconomic Factors, population characteristics, Observational study, 0305 other medical science, business, Medicaid, human activities
Abstract: OBJECTIVE: To examine characteristics that are associated with receipt of Aid and Attendance (A&A), an enhanced pension benefit for Veterans who qualify on the basis of needing daily assistance, among Veterans who receive pensions. DATA SOURCES: Secondary data analysis of 2016‐2017 national VA administrative data linked with Medicare claims. STUDY DESIGN: Observational study examining sociodemographic, medical, and healthcare utilization characteristics associated with receipt of A&A among Veterans receiving pension. PRINCIPAL FINDINGS: In 2017, 9.7% of Veterans with pension newly received the A&A benefit. The probability of receiving A&A among black and Hispanic pensioners was 4.6 percentage points lower than for white pensioners (95%CI = −0.051, −0.042). Married Veterans receiving pension had a 4.4‐percentage point higher probability of receiving A&A (95%CI = 0.039, 0.048). Most indicators of need for assistance (eg, home health utilization, dementia, stroke) were associated with significantly higher probabilities of receiving A&A, with notable exceptions: pensioners with a diagnosis of Post‐Traumatic Stress Disorder (marginal effect = −0.029 95%CI = −0.037, −0.021) or enrolled in Medicaid (marginal effect = −0.053, 95%CI = −0.057, −0.050) had lower probabilities of receiving A&A. Unadjusted and adjusted rates of receiving A&A among Veterans receiving pension varied by VA medical center. CONCLUSIONS: This study identified potential inequities in receipt of the A&A enhanced pension among a sample of Veterans receiving pension. Increased Veteran outreach, provider education, and VA office coordination can potentially reduce inequities in access to this benefit.
Published: 2021

24. A Monocyte/Dendritic Cell Molecular Signature of SARS-CoV-2 Related Multisystem Inflammatory Syndrome in Children (MIS-C) with Severe Myocarditis

Author: Camille de Cevins, Marine Luka, Nikaia Smith, Sonia Meynier, Aude Magérus, Francesco Carbone, Victor Garcia-Paredes, Laura Barnabei, Maxime Batignes, Alexandre Boullé, Marie-Claude Stolzenberg, Brieuc P. Pérot, Bruno Charbit, Tinhinane Fali, Vithura Pirabarakan, Boris Sorin, Quentin Riller, Ghaith Abdessalem, Maxime Beretta, Ludivine Grzelak, Pedro Goncalves, James Di Santo, Hugo Mouquet, Olivier Schwartz, Mohammed Zarhrate, Mélanie Parisot, Christine Bole-Feysot, Cécile Masson, Nicolas Cagnard, Aurelien Corneau, Camille Bruneau, Shen-Ying Zhang, Jean-Laurent Casanova, Brigitte Bader Meunier, Julien Haroche, Isabelle Melki, Mathie Lorrot, Mehdi Oualha, Florence Moulin, Damien Bonnet, Zahra Belhadjer, Mariane Leruez, Slimane Allali, Christele Gras Leguen, Loic de Pontual, Pediatric-Biocovid Study Group, Alain Fischer, Darragh Duffy, Frederic Rieux-Laucat, Julie Toubiana, and Mickaël Mathieu Ménager
Subjects: Gynecology, medicine.medical_specialty, Myocarditis, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Monocyte, education, Ethics committee, medicine.disease, medicine.anatomical_structure, Medicine, VEGF signaling, business
Abstract: SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κ B activity, TNF-α signaling, associated with decreased gene expression of NF-κ B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology. Funding: The study was supported by the Institut National de la Sante et de la Recherche Medicale (INSERM), by the “URGENCE COVID-19” fundraising campaign of Institut Pasteur, by the Atip-Avenir, Emergence ville de Paris program and fond de dotation Janssen Horizon and by government grants managed by the Agence National de la Recherche as part of the “Investment for the Future” program (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010, Laboratoire d’Excellence ‘‘Milieu Interieur”, grant ANR-10-LABX-69-01), the Centre de Reference Deficits Immunitaires Hereditaires (CEREDIH), the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL and “CoVarImm” to DD and JDS), and by the FASTFoundation (French Friends of Sheba Tel Hashomer Hospital). The LabTech Single-Cell@Imagine is supported by the Paris Region and the “Investissements d’avenir” program through the 2019 ATF funding – Sesame Filieres PIA (Grant N°3877871).CdC is the recipient of a CIFRE-PhD (Sanofi). L.B. was a recipient of an Imagine institute PhD international program supported by the Fondation Bettencourt Schueller. L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Universite de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its“Investments for the Future” program. S.M. was a recipient of an INSERM and Institut Imagine post-doctorat program supported by the Fondation pour la Recherche Medicale (FRMN°SPF20170938825). NS was a recipient of the Pasteur-Roux-Cantarini Fellowship. VGP obtained an Imagine international PhD fellowship program supported by the Fondation Bettencourt Schueller. BPP is the recipient of an ANRS post-doctoral fellowship. Conflict of Interest: DD, FRL, JT and MMM are listed as inventors on a patent application related to this technology (European Patent Application no. EP21305197, entitled “Methods of predicting multisystem inflammatory syndrome (MIS-C) with severe myocarditis in subjects suffering from a SARS-CoV-2 infection”). Ethical Approval: The study was approved by the Ethics Committee (Comite de Protection des Personnes Ouest IV, n° DC-2017-2987).
Published: 2021

25. Concurrent Hospice Care and Cancer-Directed Treatment for Advanced Lung Cancer and Receipt of Aggressive Care at the End of Life in the Veteran's Health Administration

Author: Tracy Shamas, Weiwei Zhu, Cary P. Gross, Cari Levy, Carolyn J Presley, Ling Han, Karl A. Lorenz, John R. O'Leary, Vincent Mor, Emily Corneau, Herta Chao, and Michal G. Rose
Subjects: medicine.medical_specialty, Aggressive care, Lung Neoplasms, Health administration, 03 medical and health sciences, 0302 clinical medicine, Quality of life (healthcare), 030502 gerontology, Carcinoma, Non-Small-Cell Lung, Medicine, Humans, Intensive care medicine, Lung cancer, General Nursing, Hospice care, health care economics and organizations, Retrospective Studies, Veterans, Receipt, Terminal Care, business.industry, Cancer, Correction, General Medicine, Original Articles, medicine.disease, humanities, respiratory tract diseases, Death, Anesthesiology and Pain Medicine, Hospice Care, 030220 oncology & carcinogenesis, 0305 other medical science, business, Stage iv
Abstract: Background: Aggressive care at the end of life (EOL) is a persistent issue for patients with stage IV nonsmall cell lung cancer (NSCLC). We evaluated the use of concurrent care (CC) with hospice care and cancer-directed treatment simultaneously within the Veteran's Health Administration (VHA) and aggressive care at the EOL. Objective: To determine whether VHA facility-level CC is associated with changes in aggressive care at the EOL. Design/Setting: Veterans with stage IV NSCLC who died between 2006 and 2012 and received lung cancer care within the VHA. Measurements: The primary outcome was aggressive care at EOL (i.e., hospital admissions, chemotherapy, and intensive care unit) within the last month of life. To compare aggressive care across VHA facilities, we used a random intercept multilevel logistic regression model to examine the association between facility-level CC within each study year (
Published: 2020

26. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients

Author: Aurélien Corneau, David Veyer, Tali Anne Szwebel, Nicolas Roche, Bruno Charbit, Darragh Duffy, Laura Barnabei, Hélène Péré, Flore Rozenberg, Nathalie Marin, Vincent Bondet, Benjamin Terrier, Pierre-Louis Tharaux, Solen Kernéis, Nader Yatim, Jeremy Boussier, Nikaïa Smith, Sarah H. Merkling, Alain Fischer, Nicolas Carlier, Frédéric Rieux-Laucat, Jean-Marc Treluyer, Camille Chenevier-Gobeaux, Paul Breillat, Rémy Gauzit, Luc Mouthon, Frédéric Pène, Jérôme Hadjadj, Caroline Morbieu, Catherine Blanc, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Laboratoire de Virologie [Hôpital Européen Georges Pompidou - APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Institut Pasteur [Paris] (IP), Diagnostic biologique automatisé [AP-HP Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pneumologie [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Unité Equipe mobile d'Infectiologie [AP-HP Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Unité de Soins Intensifs [CHU Cochin], Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service de Virologie [CHU Cochin], Département d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP], CHU Necker - Enfants Malades [AP-HP], Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Epidémiologie et modélisation de la résistance aux antimicrobiens - Epidemiology and modelling of bacterial escape to antimicrobials (EMAE), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], This study was supported by the Fonds IMMUNOV, for Innovation in Immunopathology. The study was also supported by the Institut National de la Santé et de la Recherche Médicale (INSERM) and the Institut Pasteur, by a government grant managed by the Agence National de la Recherche as part of the 'Investment for the Future' program (ANR-10-IAHU-01 and the Laboratoire d’Excellence ‘‘Milieu Intérieur', grant no. ANR-10-LABX-69-01), and by a grant from the Agence National de la Recherche (ANR-flash Covid19 'AIROCovid' to FRL and 'CoVarImm' to DD), and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). J.H. is a recipient of an Institut Imagine MD-PhD fellowship program supported by the Fondation Bettencourt Schueller. L.B. is supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) program of the Université de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its 'Investments for the Future' program., We acknowledge all health-care workers involved in the diagnosis and treatment of patients in Cochin Hospital, especially C. Azoulay L. Beaudeau, E. Canoui, P. Cohen, A. Contejean, B. Dunogué, D.Journois, P. Legendre, J. Marey and A. Régent. We thank Y. Gaudin for his advices on viral mechanism. We thank all the patients, supporters and our families for their confidence in our work., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), ANR-10-LABX-0069,MILIEU INTERIEUR,GENETIC & ENVIRONMENTAL CONTROL OF IMMUNE PHENOTYPE VARIANCE: ESTABLISHING A PATH TOWARDS PERSONALIZED MEDICINE(2010), Centre National de Référence Maladies auto-immunes Systémiques Rares [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Pasteur [Paris], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Chaire Médecine expérimentale (A. Fischer)
Subjects: Male, 0302 clinical medicine, Interferon, T-Lymphocyte Subsets, 0303 health sciences, Multidisciplinary, biology, NF-kappa B, Interleukin, Middle Aged, Viral Load, 3. Good health, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, Female, medicine.symptom, Coronavirus Infections, Viral load, medicine.drug, Signal Transduction, Adult, Critical Illness, Pneumonia, Viral, Alpha interferon, Inflammation, Interferon alpha-2, 03 medical and health sciences, Betacoronavirus, Immune system, medicine, Humans, Interleukin 6, Pandemics, 030304 developmental biology, Aged, business.industry, Interleukin-6, SARS-CoV-2, Tumor Necrosis Factor-alpha, Gene Expression Profiling, COVID-19, Interferon-alpha, Interferon-beta, Immunity, Innate, Cross-Sectional Studies, Immunology, biology.protein, business
Abstract: Interferons interfere with lung repair Interferons (IFNs) are central to antiviral immunity. Viral recognition elicits IFN production, which in turn triggers the transcription of IFN-stimulated genes (ISGs), which engage in various antiviral functions. Type I IFNs (IFN-α and IFN-β) are widely expressed and can result in immunopathology during viral infections. By contrast, type III IFN (IFN-λ) responses are primarily restricted to mucosal surfaces and are thought to confer antiviral protection without driving damaging proinflammatory responses. Accordingly, IFN-λ has been proposed as a therapeutic in coronavirus disease 2019 (COVID-19) and other such viral respiratory diseases (see the Perspective by Grajales-Reyes and Colonna). Broggi et al. report that COVID-19 patient morbidity correlates with the high expression of type I and III IFNs in the lung. Furthermore, IFN-λ secreted by dendritic cells in the lungs of mice exposed to synthetic viral RNA causes damage to the lung epithelium, which increases susceptibility to lethal bacterial superinfections. Similarly, using a mouse model of influenza infection, Major et al. found that IFN signaling (especially IFN-λ) hampers lung repair by inducing p53 and inhibiting epithelial proliferation and differentiation. Complicating this picture, Hadjadj et al. observed that peripheral blood immune cells from severe and critical COVID-19 patients have diminished type I IFN and enhanced proinflammatory interleukin-6– and tumor necrosis factor-α–fueled responses. This suggests that in contrast to local production, systemic production of IFNs may be beneficial. The results of this trio of studies suggest that the location, timing, and duration of IFN exposure are critical parameters underlying the success or failure of therapeutics for viral respiratory infections. Science , this issue p. 706 , p. 712 , p. 718 ; see also p. 626
Published: 2020

27. Associations Between Nutrition Knowledge and Overall Diet Quality: The Moderating Role of Sociodemographic Characteristics-Results From the PREDISE Study

Author: Marie-France Langlois, Louise Corneau, Julie Houle, Charles Couillard, Elise Carbonneau, Luc G. Pelletier, Simone Lemieux, Benoît Lamarche, Luigi Bouchard, Catherine Bégin, Mathieu Bélanger, Véronique Provencher, Marie-Claude Vohl, Julie Robitaille, and Sophie Desroches
Subjects: Adult, Male, Canada, Health (social science), 030309 nutrition & dietetics, 030209 endocrinology & metabolism, Diet Surveys, Nutrition knowledge, Nutrition Policy, 03 medical and health sciences, 0302 clinical medicine, Environmental health, Medicine, Humans, Child, 2. Zero hunger, 0303 health sciences, business.industry, Public Health, Environmental and Occupational Health, Quebec, Diet, Cross-Sectional Studies, Diet quality, Marital status, Female, business
Abstract: Purpose: To assess how nutrition knowledge is associated with global diet quality and to investigate whether sociodemographic characteristics (ie, sex, age, education, income, marital status, and living with children or not) moderate this association. Design: Cross-sectional web-based study. Participants: The PREDISE study aims at identifying correlates of adherence to healthy eating guidelines in French-speaking adults from the Province of Quebec, Canada. Subjects: A probability sample of 1092 participants (50% female). Measures: The Nutrition Knowledge Questionnaire and 24-hour food recalls from which the Canadian Healthy Eating Index (C-HEI) was calculated. Analysis: Multiple linear regressions performed to assess how nutrition knowledge is associated with the C-HEI. Interaction terms tested to evaluate whether sociodemographic characteristics moderate the association between nutrition knowledge and the C-HEI. Results: Nutrition knowledge (B = 0.141 [95% CI: 0.075-0.208], P < .0001) was identified as a significant correlate of the C-HEI. Education significantly moderated the association between nutrition knowledge and the C-HEI ( P interaction = .0038), with a significative association among participants with a lower education level (B = 0.295 [95% CI: 0.170-0.421], P < .0001) but not among participants with a higher education level (B = 0.077 [95% CI: −0.004 to 0.157], P = .06). Whether participants lived with or without children also significantly moderated the association ( P interaction = 0.0043); nutrition knowledge was associated with the C-HEI only in participants who were not living with children (B = 0.261 [95% CI: 0.167 to 0.355], P < .0001). Conclusion: This study suggests that the association between nutrition knowledge and adherence to healthy eating guidelines is not the same in different subgroups of the population. Interventions aiming at increasing nutrition knowledge may be a promising approach to improve diet quality, especially among individuals with a lower education.
Published: 2020

28. Immune phenotyping of Erdheim-Chester disease through mass cytometry highlights decreased proportion of non-classical monocytes and increased proportion of Th17 cells

Author: Olivier Hermine, Aurélien Corneau, Jean-François Emile, Makoto Miyara, Fleur Cohen-Aubart, Thiago Trovati Maciel, Zahir Amoura, Brice Robin, Matthias Papo, Catherine Blanc, Julien Haroche, UPMC - Faculté de médecine Pitié Salpétrière, Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Erdheim-Chester Disease, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, genetic structures, medicine.medical_treatment, Immunology, Inflammation, medicine.disease_cause, Monocytes, General Biochemistry, Genetics and Molecular Biology, Immunophenotyping, Autoimmunity, Proinflammatory cytokine, 03 medical and health sciences, 0302 clinical medicine, Immune system, Rheumatology, medicine, Humans, Immunology and Allergy, Histiocyte, ComputingMilieux_MISCELLANEOUS, 030203 arthritis & rheumatology, business.industry, Flow Cytometry, medicine.disease, 3. Good health, Histiocytosis, 030104 developmental biology, Cytokine, Erdheim–Chester disease, Th17 Cells, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Erdheim-Chester disease (ECD) is an histiocytosis of the L-group, characterised by multiorgan infiltration of histiocytes that often carry oncogenic mutations.1 In the past few years, several studies have progressively and carefully mapped ECD genome, and several mutations have been described, most of them activating the mitogen-activated protein kinases (MAPK) pathway.1 These discoveries led to new therapies targeting BRAF or MEK in patients with ECD.2 Despite these findings, ECD pathogenesis still remains undetermined. Patients with ECD present a systemic inflammatory disease, with not only macrophages but also several other immune cells infiltrating affected tissues. A few studies have tried to explore the immune phenotype of ECD, with cytokine dosage in plasma and/or immunohistochemistry analysis, suggesting a complex network of inflammatory cytokines and chemokines.3 In order to explore the inflammatory phenotype of ECD, we realised immune phenotyping of circulating immune cells of 13 patients with ECD (details on patients’ characteristics are available in online supplementary table 1) and …
Published: 2020

29. Caregiver mental health in pediatric oncology: A three-tiered model of supports

Author: Kendra R. Parris, Dawn E Corneau-Dia, D. Andrew Elliott, Erin Turner, and Brittany Barnett
Subjects: medicine.medical_specialty, Telemedicine, business.industry, Psycho-oncology, Cancer, Experimental and Cognitive Psychology, Burnout, medicine.disease, Mental health, Psychiatry and Mental health, Oncology, Family medicine, Pediatric oncology, medicine, business
Published: 2020

30. Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

Author: Hélène Péré, Laura Barnabei, Luc Mouthon, Bruno Charbit, Jérôme Hadjadj, Nathalie Marin, Vincent Bondet, Jean-Marc Treluyer, Darragh Duffy, Aurélien Corneau, Caroline Morbieu, Remy Gauzit, Nader Yatim, Nikaïa Smith, Pierre-Louis Tharaux, Frédéric Rieux-Laucat, Camille Chenevier-Gobeaux, Tali-Anne Szwebel, Alain Fischer, Jeremy Boussier, Benjamin Terrier, Nicolas Carlier, Catherine Blanc, Paul Breillat, Frédéric Pène, Flore Rozenberg, Sarah H. Merkling, Nicolas Roche, Solen Kernéis, and David Veyer
Subjects: 0303 health sciences, Chemokine, education.field_of_study, Innate immune system, biology, business.industry, medicine.medical_treatment, Population, Interleukin, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Immune system, Cytokine, Interferon, 030220 oncology & carcinogenesis, Immunology, biology.protein, Medicine, Tumor necrosis factor alpha, business, education, 030304 developmental biology, medicine.drug
Abstract: BackgroundCoronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It is characterized by distinct patterns of disease progression implying a diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known.MethodsWe performed an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic and cytokine quantification on a cohort of fifty Covid19 patients with a spectrum of disease severity. All patient were tested 8 to 12 days following first symptoms and in absence of anti-inflammatory therapy.ResultsA unique phenotype in severe and critically ill patients was identified. It consists in a profoundly impaired interferon (IFN) type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. This was associated with a persistent blood virus load and an exacerbated inflammatory response that was partially driven by the transcriptional factor NFĸB. It was also characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling as well as increased innate immune chemokines.ConclusionWe propose that type-I IFN deficiency in the blood is a hallmark of severe Covid-19 and could identify and define a high-risk population. Our study provides a rationale for testing IFN administration combined with adapted anti-inflammatory therapy targeting IL-6 or TNF-α in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.
Published: 2020
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31. Survival and Inactivation by Advanced Oxidative Process of Foodborne Viruses in Model Low-Moisture Foods

Author: Forest Dussault, Nathalie Corneau, Sabah Bidawid, Angela Chen, Neda Nasheri, and Jennifer Harlow
Subjects: Virus quantification, Infectivity, Feline calicivirus, Transmission (medicine), ved/biology, viruses, Infectious dose, ved/biology.organism_classification_rank.species, Biology, medicine.disease_cause, biology.organism_classification, Norovirus, medicine, Vaporized hydrogen peroxide, Food science, Murine norovirus
Abstract: Enteric viruses, such as human norovirus (NoV) and hepatitis A virus (HAV), are the major causes of foodborne illnesses worldwide. These viruses are shed in high numbers, have low infectious dose, and may remain infectious for weeks in the environment and food. While numerous viral survival studies have been conducted in fresh fruits and produce, limited information is available regarding viral survival and transmission in low moisture foods (LMF). LMFs are generally considered as ready-to-eat products, which undergo no or minimal pathogen reduction steps. However, numerous foodborne outbreaks associated with LMFs have been reported in recent years. The objective of this study was to examine the survival of foodborne viruses in LMFs during long-term storage at ambient temperature and to evaluate the efficacy of advanced oxidative process (AOP) treatment in the inactivation of these viruses. For this purpose, select LMFs such as pistachios, chocolate, and cereal were inoculated with HAV and the norovirus surrogates, murine norovirus (MNV) and feline calicivirus (FCV), then viral survival on these food matrices was measured over a four-week incubation at ambient temperature, by both plaque assay and droplet-digital RT-PCR (ddRT-PCR). We observed an approximately 0.5 log reduction in viral genome copies, and 1 log reduction in viral infectivity for all three tested viruses following storage of select inoculated LMFs for 4 weeks. Therefore, the present study shows that foodborne viruses can persist for long-time in LMFs. Next, we examined the inactivation efficacy of AOP treatment, which combines UV-C, ozone, and hydrogen peroxide vapor, and observed that while approximately 100% inactivation can be achieved for FCV, MNV, and HAV in chocolate, the inactivation efficiency diminishes to approximately 90% in pistachios and 70% in cereal. AOP treatment could therefore be a good candidate for the elimination of foodborne viruses from certain LMFs depending on the food matrix and surface of treatment.ImportanceLow moisture foods have been increasingly recognized as important vehicles of foodborne pathogens. In the present study, we demonstrated that foodborne viruses remain infectious during long-term storage on select low moisture foods. In addition, we evaluated the efficacy of an advanced oxidative process in the inactivation of foodborne viruses in low moisture foods. This research will help increase the safety of low moisture foods and reduce the number of foodborne illnesses due to contaminated products.
Published: 2020

32. Phenotyping of tumor infiltrating immune cells using mass-cytometry (CyTOF)

Author: Aurélien Corneau, Pauline Maby, Jérôme Galon, Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytométrie Pitié-Salpêtrière (PASS-CYPS), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0303 health sciences, Tumor microenvironment, [SDV]Life Sciences [q-bio], 030303 biophysics, Cell, Cancer, Biology, medicine.disease, Stain, 3. Good health, 03 medical and health sciences, medicine.anatomical_structure, Immune system, medicine, Cancer research, Mass cytometry, Solid tumor, Tumor immunology, ComputingMilieux_MISCELLANEOUS
Abstract: The anti-tumor immune response plays a crucial role in cancer patient outcome as well as in response to the growing family of immunotherapeutic treatments. Improving patient prognostic and therapeutic management requires a better knowledge of the tumor microenvironment, for which a deep characterization of tumor-infiltrating immune populations is instrumental. Mass cytometry represents an excellent tool in tumor Immunology, as it allows the simultaneous analysis of >40 markers on single cells. In this chapter, we review challenging technical aspects of the mass cytometry phenotyping of tumor infiltrating immune cells, focusing on fresh human solid tumor samples. We first explain how to design mass cytometry experiments, then provide detailed protocols to isolate mononuclear immune cells from solid tissues and to stain them for an acquisition on a mass cytometer. We also discuss how to optimize the preparation of single immune cell samples, and how to ensure the reproducibility of data generated from distinct fresh human samples. Finally, we provide troubleshooting suggestions for difficult sample acquisitions on a mass cytometer.
Published: 2020

33. Que la lumière soit. Et si ce n’était plus seulement vrai !

Author: Aurélien Corneau, Catherine Blanc, Thierry Idziorek, Pierre Bourdely, Julie Cazareth, and Nathalie Jouy
Subjects: 0301 basic medicine, Physics, 03 medical and health sciences, 030104 developmental biology, medicine.diagnostic_test, medicine, Mass cytometry, General Medicine, Computational biology, Cytometry, General Biochemistry, Genetics and Molecular Biology, Flow cytometry
Abstract: Ces dernières années ont vu une progression importante des capacités des nouveaux appareils de cytométrie. Deux sauts technologiques ont été récemment franchis avec la cytométrie couplée à la spectrométrie de masse, dans laquelle les fluorochromes ont été remplacés par des métaux rares non radioactifs de la famille des lanthanides et la cytométrie spectrale qui collecte les photons sur le spectre visible. Dans cette revue, nous décrivons schématiquement la cytométrie en flux conventionnelle et ces deux technologies ainsi que leurs avantages et adaptabilités et leurs inconvénients.
Published: 2018

34. Assessing the differential impacts of online, mixed, and offline gambling

Author: Elisabeth Papineau, Serge Sévigny, Guy Lacroix, N. Corneau-Tremblay, Fanny Lemetayer, and Jean-François Biron
Subjects: medicine.medical_specialty, education.field_of_study, media_common.quotation_subject, Public health, Population, 030508 substance abuse, Online gambling, Sample (statistics), Differential (mechanical device), Neglect, 03 medical and health sciences, 0302 clinical medicine, Propensity score matching, medicine, 0305 other medical science, Psychology, education, Psychosocial, Social psychology, 030217 neurology & neurosurgery, Applied Psychology, media_common
Abstract: The emergence of new behaviours associated with communication technologies has prompted questions about the evolution of gambling in the population. The development of online gambling gave rise to public health concerns back 20 years ago. Current knowledge indicates that online gamblers generally tend to show more psychosocial problems than offline gamblers. But those portraits tend to neglect the differences between pure and mixed online gamblers. The goal of this research is to assess if, and to what extent, online gambling generates more harmful impacts on the health and well-being in a sample of adult gamblers in Quebec. The propensity score matching method was chosen to assess the variable prevalence of impacts on a sample of 810 regular gamblers recruited from an online panel. They were divided into sub-groups: pure online gamblers (n = 143), mixed online gamblers (n = 125), and a control group of offline gamblers (n = 542). The study has revealed that among online gamblers and their entoura...
Published: 2017

35. Contentions mécaniques en psychiatrie : étude phénoménologique de l’expérience vécue du personnel infirmier

Author: Dave Holmes, Jean Daniel Jacob, Désiré Rioux, and Pascale Corneau
Subjects: medicine.medical_specialty, 030504 nursing, Interpretative phenomenological analysis, Practice patterns, Lived experience, Health knowledge, General Medicine, medicine.disease_cause, 030227 psychiatry, Comprehension, 03 medical and health sciences, 0302 clinical medicine, Intervention (counseling), medicine, Psychological stress, 0305 other medical science, Psychology, Psychiatry, Qualitative research
Abstract: The use of mechanical restraints in psychiatric settings is currently the subject of ethical controversy. However, both patients' and nurses' voices are absent in the debate over this controversial intervention. The objective of this qualitative study was to examine the experience of psychiatric nurses using mechanical restraints. Twentyone nurses working on either the acute psychiatric inpatient unit and/or the emergency psychiatric unit of a university affiliated Canadian hospital participated in semi-structured interviews, which were then transcribed, coded and analyzed using the interpretative phenomenological analysis (IPA) method. Three main themes were identified : 1) Practice setting ; 2) Mechanical restraint process ; and 3) Resorting to mechanical restraints. These results highlight the organizational and emotional challenges faced by psychiatric nurses. Foucault and Goffman's work were the primary theoretical sources that guided the critical analysis of this qualitative research.
Published: 2017

36. Development and validation of a nutrition knowledge questionnaire for a Canadian population

Author: Catherine Bégin, Simone Lemieux, Julie Robitaille, Sophie Desroches, Louise Corneau, Marie-Claude Vohl, Elise Carbonneau, Véronique Provencher, and Maude Bradette-Laplante
Subjects: Adult, Male, 0301 basic medicine, Health Knowledge, Attitudes, Practice, medicine.medical_specialty, Adolescent, Medicine (miscellaneous), Sample (statistics), Body Mass Index, Nutrition Policy, Young Adult, 03 medical and health sciences, Cronbach's alpha, Surveys and Questionnaires, Canada's Food Guide, Content validity, medicine, Humans, Nutritionists, Reliability (statistics), Aged, Face validity, 030109 nutrition & dietetics, Nutrition and Dietetics, Quebec, Public Health, Environmental and Occupational Health, Reproducibility of Results, Construct validity, Middle Aged, Research Papers, Exploratory factor analysis, Socioeconomic Factors, Family medicine, Female, Psychology
Abstract: ObjectiveThe present study aimed to develop and validate a nutrition knowledge questionnaire in a sample of French Canadians from the province of Quebec, taking into account dietary guidelines.DesignA thirty-eight-item questionnaire was developed by the research team and evaluated for content validity by an expert panel, and then administered to respondents. Face validity and construct validity were measured in a pre-test. Exploratory factor analysis and covariance structure analysis were performed to verify the structure of the questionnaire and identify problematic items. Internal consistency and test–retest reliability were evaluated through a validation study.SettingOnline survey.SubjectsSix nutrition and psychology experts, fifteen registered dietitians (RD) and 180 lay people participated.ResultsContent validity evaluation resulted in the removal of two items and reformulation of one item. Following face validity, one item was reformulated. Construct validity was found to be adequate, with higher scores for RDv. non-RD (21·5 (sd2·1)v. 15·7 (sd3·0) out of 24,Pα=0·73). Assessment of test–retest reliability resulted in significant associations for the total knowledge score (r=0·59,PConclusionsThis nutrition knowledge questionnaire was found to be a suitable instrument which can be used to measure levels of nutrition knowledge in a Canadian population. It could also serve as a model for the development of similar instruments in other populations.
Published: 2016

37. Is the Canadian Healthy Eating Index 2007 an Appropriate Diet Indicator of Metabolic Health? Insights from Dietary Pattern Analysis in the PREDISE Study

Author: Simone Lemieux, Jacynthe Lafrenière, Louise Corneau, Elise Carbonneau, Julie Robitaille, Marie-Ève Labonté, Catherine Laramée, and Benoît Lamarche
Subjects: Adult, Male, 0301 basic medicine, Canada, Multivariate statistics, Index (economics), Binomial regression, diet quality score, lcsh:TX341-641, 030209 endocrinology & metabolism, Healthy eating, Alternative Healthy Eating Index, Diet Surveys, Article, 03 medical and health sciences, 0302 clinical medicine, Prevalence, Humans, Medicine, Healthy Eating Index, dietary guidelines, Aged, Metabolic health, Metabolic Syndrome, 2. Zero hunger, 030109 nutrition & dietetics, Nutrition and Dietetics, business.industry, Feeding Behavior, Middle Aged, Dietary pattern, medicine.disease, Confidence interval, Cross-Sectional Studies, Nutrition Assessment, Female, dietary pattern, Diet, Healthy, Metabolic syndrome, business, lcsh:Nutrition. Foods and food supply, Food Science, Demography
Abstract: The objective of this study was to identify key elements from the 2007 Canada&rsquo, s Food Guide that should be included in a diet quality score aiming to reflect the risk of metabolic syndrome (MetS). Dietary intakes of 998 adults (mean age: 43.2 years, 50% women) were used to obtain the Canadian Healthy Eating Index 2007 (C-HEI 2007) and Alternative Healthy Eating Index 2010 (AHEI) scores, as well as a dietary pattern (DP) generated by the reduced rank regression (RRR) method. Based on these three scores, a modified version of the C-HEI 2007 (Modified C-HEI) was then proposed. The prevalence ratio (PR) of MetS was examined across diet quality scores using multivariate binomial regression analysis. A higher AHEI, Modified C-HEI, and a lower score for DP were all associated with a significantly lower prevalence of MetS (PR = 0.42, 95% confidence interval (CI) 0.28, 0.64, PR = 0.39, 95% CI 0.23, 0.63, and PR = 0.48, 95% CI 0.31, 0.74, respectively), whereas C-HEI 2007 was not (PR = 0.68, 95% CI 0.47, 1.00). Results suggest that a Modified C-HEI that considers key elements from the C-HEI 2007 and the AHEI, as well the DP, shows that participants with a higher score are less likely to have MetS.
Published: 2019
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38. UM171 induces a homeostatic inflammatory-detoxification response supporting human HSC self-renewal

Author: Nadine Mayotte, Guy Sauvageau, Simon Girard, Sophie Corneau, Tara MacRae, Laura Simon, Iman Fares, Jean-François Spinella, Elisa Tomellini, Jalila Chagraoui, and Bernhard Lehnertz
Subjects: 0301 basic medicine, Indoles, Physiology, Cellular differentiation, Gene Expression, Pathology and Laboratory Medicine, Toxicology, Biochemistry, 0302 clinical medicine, Spectrum Analysis Techniques, Animal Cells, Immune Physiology, Medicine and Health Sciences, Homeostasis, Cell Self Renewal, Immune Response, Innate Immune System, Multidisciplinary, Chemistry, Stem Cells, Hematopoietic stem cell, Cell Differentiation, Neurochemistry, Flow Cytometry, 3. Good health, Cell biology, Haematopoiesis, medicine.anatomical_structure, Spectrophotometry, 030220 oncology & carcinogenesis, Medicine, Cytokines, Cytophotometry, medicine.symptom, Stem cell, Cellular Types, Neurochemicals, Detoxification, Adult stem cell, Signal Transduction, Research Article, Science, Immunology, Inflammation, Research and Analysis Methods, Nitric Oxide, 03 medical and health sciences, Signs and Symptoms, Downregulation and upregulation, Diagnostic Medicine, medicine, Genetics, Humans, Cell Proliferation, Blood Cells, Cell growth, Gene Expression Profiling, Biology and Life Sciences, Cell Biology, Molecular Development, Hematopoietic Stem Cells, 030104 developmental biology, Pyrimidines, Immune System, Metabolic Detoxication, Phase I, Reactive Oxygen Species, Transcriptome, Biomarkers, Developmental Biology, Neuroscience
Abstract: Elucidation of the molecular cues required to balance adult stem cell self-renewal and differentiation is critical for advancing cellular therapies. Herein, we report that the hematopoietic stem cell (HSC) self-renewal agonist UM171 triggers a balanced pro- and anti-inflammatory/detoxification network that relies on NFKB activation and protein C receptor-dependent ROS detoxification, respectively. We demonstrate that within this network, EPCR serves as a critical protective component as its deletion hypersensitizes primitive hematopoietic cells to pro-inflammatory signals and ROS accumulation resulting in compromised stem cell function. Conversely, abrogation of the pro-inflammatory activity of UM171 through treatment with dexamethasone, cAMP elevating agents or NFkB inhibitors abolishes EPCR upregulation and HSC expansion. Together, these results show that UM171 stimulates ex vivo HSC expansion by establishing a critical balance between key pro- and anti-inflammatory mediators of self-renewal.
Published: 2019

39. CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Author: D. Amelin, Aurélien Corneau, Catherine Blanc, Kuberaka Mariampillai, Gaëlle Dzangué-Tchoupou, Yves Allenbach, Wladimir Mauhin, Loïs Bolko, Olivier Benveniste, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Plateforme Cytométrie Pitié-Salpêtrière (LUMIC-CYPS), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Cytométrie Pitié-Salpêtrière (PASS-CYPS), Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Centre de Recherche en Myologie, Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), and CHU Pitié-Salpêtrière [APHP]
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV]Life Sciences [q-bio], Immunology, Population, Physiopathology, chemical and pharmacologic phenomena, CD38, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, Mass cytometry, education, Interleukin-7 receptor, ComputingMilieux_MISCELLANEOUS, Myositis, 030304 developmental biology, 0303 health sciences, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, medicine.disease, 3. Good health, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV] Life Sciences [q-bio], [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, CD8+ T-bet+ cells, Biomarker (medicine), [SDV.IMM]Life Sciences [q-bio]/Immunology, Inclusion body myositis, business, Deep immune profiling, 030217 neurology & neurosurgery, CD8, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious. Objectives Our aim was to deepen our understanding of the immune mechanisms involved in inclusion body myositis and identify specific biomarkers. Methods Using a panel of thirty-six markers and mass cytometry, we performed deep immune profiling of peripheral blood cells from inclusion body myositis patients and healthy donors, divided into two cohorts: test and validation cohorts. Potential biomarkers were compared to myositis controls (anti-Jo1-, anti-3-hydroxyl-3-methylglutaryl CoA reductase-, and anti-signal recognition particle-positive patients). Results Unsupervised analyses revealed substantial changes only within CD8+ cells. We observed an increase in the frequency of CD8+ cells that expressed high levels of T-bet, and containing mainly both effector and terminally differentiated memory cells. The senescent marker CD57 was overexpressed in CD8+T-bet+ cells of inclusion body myositis patients. As expected, senescent CD8+T-bet+ CD57+ cells of both patients and healthy donors were CD28nullCD27nullCD127null. Surprisingly, non-senescent CD8+T-bet+ CD57- cells in inclusion body myositis patients expressed lower levels of CD28, CD27, and CD127, and expressed higher levels of CD38 and HLA-DR compared to healthy donors. Using classification and regression trees alongside receiver operating characteristics curves, we identified and validated a frequency of CD8+T-bet+ cells >51.5% as a diagnostic biomarker specific to inclusion body myositis, compared to myositis control patients, with a sensitivity of 94.4%, a specificity of 88.5%, and an area under the curve of 0.97. Conclusion Using a panel of thirty-six markers by mass cytometry, we identify an activated cell population (CD8+T-bet+ CD57- CD28lowCD27lowCD127low CD38+ HLA-DR+) which could play a role in the physiopathology of inclusion body myositis, and identify CD8+T-bet+ cells as a predominant biomarker of this disease.
Published: 2019

40. Association of Expanded VA Hospice Care With Aggressive Care and Cost for Veterans With Advanced Lung Cancer

Author: Risha Gidwani-Marszowski, Nina R. Joyce, Bruce Kinosian, Emily Corneau, Scott Shreve, Todd H. Wagner, Karl A. Lorenz, Cari Levy, Vincent Mor, Mary Ersek, Susan C. Miller, and Katherine E. Faricy-Anderson
Subjects: Male, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Databases, Factual, Hospitals, Veterans, Pharmacy, Article, law.invention, 03 medical and health sciences, 0302 clinical medicine, Cost of Illness, law, medicine, Humans, Registries, 030212 general & internal medicine, Lung cancer, Veterans Affairs, Aged, Veterans, Aged, 80 and over, business.industry, Palliative Care, Hospices, Cancer, Health Care Costs, Odds ratio, medicine.disease, Intensive care unit, Hospice Care, Oncology, 030220 oncology & carcinogenesis, Emergency medicine, Medicare Hospice, Female, Observational study, business
Abstract: Importance Medicare hospice beneficiaries discontinue disease-modifying treatments because the hospice benefit limits access. While veterans have concurrent access to hospice care and Veterans Affairs (VA) Medical Center (VAMC)-provided treatments, the association of this with changes in treatment and costs of veterans’ end-of-life care is unknown. Objective To determine whether increasing availability of hospice care, without restrictions on disease-modifying treatments, is associated with reduced aggressive treatments and medical care costs at the end of life. Design, Setting, and Participants A modified difference-in-differences study design, using facility fixed effects, compared patient outcomes during years with relatively high vs lower hospice use. This study evaluated 13 085 veterans newly diagnosed with stage IV non–small cell lung cancer (NSCLC) from 113 VAMCs with a minimum of 5 veterans diagnosed with stage IV NSCLC per year, between 2006 and 2012. Data analyses were conducted between January 2017 and July 2018. Exposures Using VA inpatient, outpatient, pharmacy claims, and similar Medicare data, we created VAMC-level annual aggregates of all patients who died of cancer for hospice use, cancer treatment, and/or concurrent receipt of both in the last month of life, dividing all VAMC years into quintiles of exposure to hospice availability. Main Outcomes and Measures Receipt of aggressive treatments (2 or more hospital admissions within 30 days, tube feeding, mechanical ventilation, intensive care unit [ICU] admission) and total costs in the first 6 months after diagnosis. Results Of the 13 085 veterans included in the study, 12 858 (98%) were men; 10 531 (81%) were white, and 5949 (46%) were older than 65 years. Veterans with NSCLC treated in a VAMC in the top hospice quintile (79% hospice users), relative to the bottom quintile (55% hospice users), were more than twice as likely to have concurrent cancer treatment after initiating hospice care (adjusted odds ratio [AOR], 2.28; 95% CI, 1.67-3.31). Nonetheless, for veterans with NSCLC seen in VAMCs in the top hospice quintile, the AOR of receiving aggressive treatment in the 6 months after diagnosis was 0.66 (95% CI, 0.53-0.81), and the AOR of ICU use was 0.78 (95% CI, 0.62-0.99) relative to patients seen in VAMCs in the bottom hospice quintile. The 6-month costs were lower by an estimated $266 (95% CI, −$358 to −$164) per day for the high-quintile group vs the low-quintile group. There was no survival difference. Conclusions and Relevance Increasing the availability of hospice care without restricting treatment access for veterans with advanced lung cancer was associated with less aggressive medical treatment and significantly lower costs while still providing cancer treatment.
Published: 2019

41. Complex karyotype AML displays G2/M signature and hypersensitivity to PLK1 inhibition

Author: Yves Gareau, Anne Marinier, Céline Moison, Sébastien Lemieux, Melanie Frechette, Nadine Mayotte, Josée Hébert, Bernhard Lehnertz, Sophie Corneau, Clarisse Thiollier, Vincent-Philippe Lavallée, Sylvie Lavallée, Guy Sauvageau, Valérie Blouin-Chagnon, and Isabel Boivin
Subjects: Adult, Male, Myeloid, Karyotype, Cell Cycle Proteins, Protein Serine-Threonine Kinases, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, Mice, Young Adult, 0302 clinical medicine, hemic and lymphatic diseases, Cell Line, Tumor, Proto-Oncogene Proteins, Complex Karyotype, medicine, Animals, Humans, neoplasms, Protein Kinase Inhibitors, Aged, Aged, 80 and over, Myeloid Neoplasia, business.industry, Myelodysplastic syndromes, Pteridines, Myeloid leukemia, Volasertib, Hematology, Middle Aged, medicine.disease, PTPN11, G2 Phase Cell Cycle Checkpoints, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, Cancer research, M Phase Cell Cycle Checkpoints, Female, KRAS, Tumor Suppressor Protein p53, business, 030215 immunology
Abstract: Patients diagnosed with acute myeloid leukemia with complex karyotype (CK AML) have an adverse prognosis using current therapies, especially when accompanied by TP53 alterations. We hereby report the RNA-sequencing analysis of the 68 CK AML samples included in the Leucegene 415 patient cohort. We confirm the frequent occurrence of TP53 alterations in this subgroup and further characterize the allele expression profile and transcript alterations of this gene. We also document that the RAS pathway (N/KRAS, NF1, PTPN11, BRAF) is frequently altered in this disease. Targeted chemical interrogation of genetically characterized primary CK AML samples identifies polo-like kinase 1 (PLK1) inhibitors as the most selective agents for this disease subgroup. TP53 status did not alter sensitivity to PLK1 inhibitors. Interestingly, CK AML specimens display a G2/M transcriptomic signature that includes higher expression levels of PLK1 and correlates with PLK1 inhibition sensitivity. Together, our results highlight vulnerability in CK AML. In line with these in vitro data, volasertib shows a strong anti-AML activity in xenotransplantation mouse models of human adverse AML. Considering that PLK1 inhibitors are currently being investigated clinically in AML and myelodysplastic syndromes, our results provide a new rationale for PLK1-directed therapy in patients with adverse cytogenetic AML.
Published: 2019

42. Stress in Depression

Author: Maria Ditcheva, Gail Corneau, and Suzanne Vrshek-Schallhorn
Subjects: Stress (mechanics), business.industry, Medicine, Chronic stress, business, Life stress, Depression (differential diagnoses), Clinical psychology
Abstract: That life stress precipitates depression is one of the most replicated findings in psychiatric research, but prior to Brown and Harris’s seminal contributions, insufficiently rigorous methods led to underestimates of the effects of stress and threatened the field. This chapter provides a methodological and historical overview, followed by a review of evidence that recent stress predicts depression across the life span. It also examines demographic vulnerability factors and research on early adversity and depression, closing with future directions. Two themes manifest throughout. First, stress assessment that uses investigator-rated severity, accounts for severity, establishes temporal precedence, and isolates the few months prior to depression onset remains critical to progress. Second, identifying the most potent forms of stress for depression is a key question that will facilitate both preventive/intervention efforts and more powerful tests in mechanistic research. Although evidence points to interpersonal forms of stress, few studies provide the necessary direct tests.
Published: 2019

43. A novel combination of chemotherapy and immunotherapy controls tumor growth in mice with a human immune system

Author: Christine Ménétrier-Caux, Rodrigo Nalio Ramos, Pukar Kc, Gilles Marodon, Eliane Piaggio, Aude Burlion, Christophe Caux, Kelhia Sendeyo, Daniel Olive, Aurélien Corneau, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Immunité et cancer (U932), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé (PASS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Cytométrie Pitié-Salpêtrière (LUMIC-CYPS), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Aix Marseille Université (AMU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centro de Informatica UFPE [Recife] (CIn), Universidade Federal de Pernambuco [Recife] (UFPE), Plateforme Cytométrie Pitié-Salpêtrière (CyPS), Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Curie, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Schering-Plough Laboratories for Immunological Research, Schering Plough Laboratories, Immunologie - Immunopathologie - Immunothérapeutique (I3), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Gestionnaire, Hal Sorbonne Université, Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Cyclophosphamide, T cell, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, chemotherapy, lcsh:RC254-282, regulatory T cells, Flow cytometry, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Immunology and Allergy, Mass cytometry, Tumor growth, 030304 developmental biology, Original Research, Chemotherapy, 0303 health sciences, Innate immune system, medicine.diagnostic_test, business.industry, Cancer, Immunotherapy, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, humanized mice, Oncology, ICOS, 030220 oncology & carcinogenesis, Cancer research, Immunogenic cell death, cyclophosphamide, immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, business, lcsh:RC581-607, CD8, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Mice reconstituted with a human immune system and bearing human tumors represent a promising model for developing novel cancer immunotherapies. Here, we used mass cytometry and multi-parametric flow cytometry to characterize human leukocytes infiltrating a human breast cancer tumor model in immunocompromised NOD.SCID.γc-null mice reconstituted with a human immune system and compared it to samples of breast cancer patients. We observed highly activated human CD4+ and CD8+ T cells in the tumor, as well as minor subsets of innate immune cells in both settings. We also report that ICOS+ CD4+ regulatory T cells (Treg) were enriched in the tumor relative to the periphery in humanized mice and patients, providing a target to affect Treg and tumor growth. Indeed, administration of a neutralizing mAb to human ICOS reduced Treg proportions and numbers and improved CD4+ T cell proliferation in humanized mice. Moreover, a combination of the anti-ICOS mAb with cyclophosphamide reduced tumor growth, and that was associated with an improved CD8 to Treg ratio. However, depletion of human CD8+ T cells only marginally affected tumor control whereas depletion of murine myeloid cells abrogated the effect of the combination therapy. Altogether, our results indicate that a combination of anti-ICOS mAb and chemotherapy controls tumor growth in humanized mice and highlight the crucial implication of innate immunity in treatment efficacy, opening new perspectives for the treatment of breast cancer.One sentence summaryICOS expressed on Tregs is a promising target to improve tumor immunity in humansAbbreviationsICOSInducible CostimulatoryNSGNOD.SCID.gc-nullTregregulatory T cellsCTXcyclophosphamideHuMicehumanized miceCyTOFcytometry time-of-flighttSNEtdistributed stochastic neighbor embeddingpDCsplasmacytoid dendritic cellsDCdendritic cellsICDimmunogenic cell death
Published: 2019

44. UM171 Induces a Homeostatic Inflammatory Response Supporting Human HSC Self-Renewal

Author: Bernhard Lehnertz, Sophie Corneau, Jean-François Spinella, Elisa Tomellini, Simon Girard, Iman Fares, Nadine Mayotte, Laura Simon, Guy Sauvageau, and Jalila Chagraoui
Subjects: CD86, Haematopoiesis, medicine.anatomical_structure, Downregulation and upregulation, Chemistry, medicine, Hematopoietic stem cell, Inflammation, medicine.symptom, Stem cell, Ex vivo, Cell biology, Adult stem cell
Abstract: Elucidation of the molecular cues required to balance adult stem cell self-renewal and differentiation is critical for advancing cellular therapies. Herein, we report that the hematopoietic stem cell (HSC) self-renewal agonist UM171 triggers a balanced pro- and anti-inflammatory/detoxification network that relies on NFKB-CD86 activation and protein C receptor-dependent ROS detoxification, respectively. We demonstrate that within this network, EPCR serves as a critical protective component as its deletion hypersensitizes primitive hematopoietic cells to pro-inflammatory signals resulting in compromised stem cell function. Conversely, abrogation of the pro-inflammatory activity of UM171 through either CD86 suppression, treatment with dexamethasone, cAMP elevating agents or NFKB inhibitors abolishes EPCR upregulation and HSC expansion. Together, these results show that UM171 stimulates ex vivo HSC expansion by establishing a critical balance between key pro- and anti-inflammatory mediators of self-renewal.
Published: 2019

45. The impact of prior day sleep and physical activity on the cortisol awakening response

Author: Gail Corneau, Laurie Wideman, Suzanne Vrshek-Schallhorn, Travis Anderson, and Kari M. Eddington
Subjects: Activity level, medicine.medical_specialty, Cortisol awakening response, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Physical activity, Audiology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, medicine, Humans, Wakefulness, Young adult, Saliva, Exercise, Biological Psychiatry, Psychoneuroendocrinology, Morning, Endocrine and Autonomic Systems, business.industry, Actigraphy, Sleep in non-human animals, Circadian Rhythm, 030227 psychiatry, Psychiatry and Mental health, Sleep Quality, Sleep, business, 030217 neurology & neurosurgery
Abstract: The cortisol awakening response (CAR) describes the increase in cortisol within the first 30–60 min after waking from nocturnal sleep, and is a common biomarker used within psychoneuroendocrinology, but the effect of sleep on the CAR is currently unclear. A previous study suggested that reported discrepancies may be due to other lifestyle behaviors such as physical activity; given the role of the CAR in energy regulation and preparation for the day, it is theoretically plausible that activity level would influence the CAR. However, no study has yet utilized objective monitoring of day-to-day sleep and physical activity to investigate potential effects on the CAR. This study aimed to test the hypotheses that either sleep duration or sleep quality would interact with the prior 24 h′ physical activity to predict the CAR on the following morning. Salivary samples were collected from 85 young adults (mean = 19.1 years, SD = 1.89) immediately after waking from nocturnal sleep and again 30 min after waking; two complete and consecutive days were used. Participants wore accelerometers (ActiGraph, wGT3X-BT) throughout this phase of a larger study, which provided objective measures of sleep duration, number of awakenings, and amount of physical activity. Mixed-effects models with post-hoc regions of significance decompositions tested the hypothesized interaction effects. Results demonstrated a significant interaction between prior day sleep duration and physical activity predicting the next day CAR, wherein short sleep duration and high levels of physical activity resulted in an augmented CAR. Although more sleep clearly predicted a smaller next day CAR in main effect, this study provides additional support that sleep duration effects are also moderated by prior day physical activity. Both behavioral factors should be considered when assessing the CAR and the association between the CAR other psychoneuroendocrine outcomes.
Published: 2021

46. Liking for foods high in salt and fat is associated with a lower diet quality but liking for foods high in sugar is not – Results from the PREDISE study

Author: Véronique Provencher, Mathieu Bélanger, Luc G. Pelletier, Simone Lemieux, Julie Houle, Louise Corneau, Rémi Rabasa-Lhoret, Catherine Bégin, Marie-Claude Vohl, Benoît Lamarche, Marie-France Langlois, Charles Couillard, Elise Carbonneau, Julie Robitaille, and Sophie Desroches
Subjects: 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, 030309 nutrition & dietetics, business.industry, digestive, oral, and skin physiology, 030209 endocrinology & metabolism, Healthy eating, Computer-assisted web interviewing, Nutrition knowledge, 03 medical and health sciences, 0302 clinical medicine, Diet quality, Environmental health, Medicine, Sugar, business, Food Science
Abstract: The research aimed at examining how liking for foods high in salt and fat and for foods high in sugar are associated with overall diet quality and how these associations differ according to individual characteristics (i.e., sex, age, education, income, nutrition knowledge, and energy reporting status) in French-speaking adults from the Province of Quebec, Canada. As part of the web-based cross-sectional PREDISE study, 1096 men and women completed online questionnaires. The Food Liking Questionnaire assessed reported liking for a variety of salty foods (high in salt and fat) and sweet foods (high in sugar and either high-fat or low-fat) on a scale from 1 to 9. The Canadian Healthy Eating Index (C-HEI) was computed based on data collected using 24-hour food recalls. Women (vs. men) reported lower liking for salty foods (5.97 ± 1.34 vs. 6.58 ± 1.16, p
Published: 2021

47. 3019 – CRISPR-BASED ENGINEERING OF A REPORTER ALLELE DEMONSTRATES THAT HLF EXPRESSION DEFINES THE HUMAN HAEMATOPOIETIC STEM CELL STATE

Author: Elisa Tomellini, Nadine Mayotte, Sophie Corneau, Tara MacRae, Guy Sauvageau, Isabel Boivin, Jalila Chagraoui, and Bernhard Lehnertz
Subjects: Cancer Research, Cell Biology, Hematology, Biology, Marker gene, Hepatic Leukemia Factor, Cell biology, Blood cell, Transplantation, Haematopoiesis, medicine.anatomical_structure, Cord blood, Genetics, medicine, CRISPR, Stem cell, Molecular Biology
Abstract: Haematopoietic stem cells (HSCs) sustain blood cell homeostasis throughout life and are able to regenerate all blood lineages following transplantation. Despite this clear functional definition, the accurate separation of human HSCs from their differentiated progeny can currently only be achieved through combinatorial measurement of multiple surface antigens. By extensive transcriptomic surveying of bulk and single-cell datasets, we have identified the master transcription factor HLF (Hepatic Leukemia Factor) as the most selective and consistently expressed marker gene in HSC-enriched sub-populations of different ontogenetic sources and ex vivo expanded CD34+ cord blood cells. To directly track its expression, we have engineered a genomic reporter strategy that relies on targeting its 3’ non-coding region with a Cas9 ribonucleoprotein complex followed by infection with a recombinant AAV6 vector providing a repair template to introduce a fluorescent gene cassette. This approach routinely achieves high reporter insertion efficiency and is capable of selectively labeling the most immature human blood cells on the basis of a single engineered parameter. Most importantly, use of this reporter demonstrates that HLF-expressing cells comprise all of the stem cell activity in culture and in vivo during serial transplantation. Taken together, our results establish HLF as the most defining gene of the human haematopoietic stem cell state and outline a next-generation approach to mark these cells in real-time with unmatched fidelity.
Published: 2020

48. AB0038 IMMUNE PHENOTYPING OF ERDHEIM-CHESTER DISEASE THROUGH MASS CYTOMETRY

Author: Zahir Amoura, Matthias Papo, Olivier Hermine, Jean-François Emile, Fleur Cohen, T. Trovati Maciel, Julien Haroche, Makoto Miyara, Aurélien Corneau, B. Robin, and Catherine Blanc
Subjects: genetic structures, biology, business.industry, Monocyte, Immunology, Inflammation, medicine.disease, Peripheral blood mononuclear cell, General Biochemistry, Genetics and Molecular Biology, Pathogenesis, Immune system, medicine.anatomical_structure, Rheumatology, Erdheim–Chester disease, medicine, biology.protein, Immunology and Allergy, Mass cytometry, medicine.symptom, Antibody, business
Abstract: Background:The understanding of Erdheim-Chester Disease (ECD) pathogenesis has been greatly improved these past few years with the discovery of activating MAPK pathway mutations in most of ECD patients. However, the inflammatory phenotype of ECD remains widely unknown.Objectives:We aimed to explore the inflammatory phenotype of Erdheim-Chester disease (ECD) using mass cytometry.Methods:We analyzed peripheral blood mononuclear cells from 13 ECD patients and 11 healthy donors (HD) using mass cytometry with 29 metal-conjugated antibodies.Results:Compared to HD, untreated ECD patients had increased proportion of classical monocytes (90.8 [87.1-96.5] vs 81.6 [76.2-87.5] %, p=0.02) and decreased proportion of non-classical monocytes (4.7 [3.4-9.7] vs 11.8 [6.6-17.2] %, p=0.047). Untreated ECD patients had more circulating Th17 cells compared to HD (3.3 [3-5.3] vs 1.3 [0.4-2.3] %, p=0.015) and ECD patients treated with BRAF or MEK inhibitors (3.3 (3-5.3] vs 1.9 [0.6-2.4] %, p=0.005). Moreover Treg cells were lower in ECD patients than HD, with an increased Th17/Treg ratio (1.37 [0.74-1.9] vs 0.34 [0.19-0.43], p=0.0004). There was no difference regarding Th1 cells, Th2 cells, B cells, NK cells and circulating dendritic cells.Conclusion:ECD monocyte profile seems similar to what have been described in CMML. Inflammation observed in ECD may be driven through Th17 cells, and might be targeted with specific treatment.Disclosure of Interests:None declared
Published: 2020

49. Aggressive care at end-of-life in the Veteran’s Health Administration versus fee-for-service Medicare among patients with advanced lung cancer

Author: Emily Corneau, Pamela R. Soulos, Weiwei Zhu, Tracy Shamas, Ling Han, Cari Levy, Karl A. Lorenz, Kiranveer Kaur, John R. O'Leary, Vincent Mor, Cary P. Gross, Herta H. Chao, Michal G. Rose, and Carolyn J Presley
Subjects: Receipt, Cancer Research, medicine.medical_specialty, Aggressive care, business.industry, medicine.disease, humanities, Cancer treatment, Health administration, Oncology, Family medicine, Medicine, business, Fee-for-service, Lung cancer, health care economics and organizations, Hospice care
Abstract: 12025 Background: The Veteran’s Health Administration (VHA) allows simultaneous receipt of cancer treatment and hospice care, termed concurrent care, while fee-for-service Medicare does not. Although many physicians who care for patients in the VHA also care for private sector patients, it is unclear whether there is a “spillover” relation between end of life (EOL) care in the VHA and Medicare systems at the regional level. We examined temporal trends, as well as regional-level associations between Medicare and VHA EOL practice for patients with advanced lung cancer. Methods: We conducted a retrospective study on VHA and SEER-Medicare (SM) decedents from 2006-2012 with stage IV non-small cell lung cancer (NSCLC) who received any lung cancer care. Aggressive care (AC) at EOL was defined as any of the following within 30 days of death– intensive care unit (ICU) admission, no-hospice care, cardiopulmonary resuscitation(CPR), mechanical ventilation (MV), > 1 inpatient admission and receipt of chemotherapy. Descriptive statistics were used to compare outcomes. We also analyzed the association between Medicare hospital referral region (HRR) hospice admissions, Medicare HRR EOL spending, and VHA AC use adjusted for patient’s characteristics using a random intercept mixed effect logistic regression model after matching VHA facilities with Medicare facilities in a particular HRR. Results: AC use significantly decreased during the study period, from 46% to 31% among 18,371 Veterans and from 42% to 38% among 25,283 in the SM cohort, (t-test P < .05). Hospice use significantly increased within both cohorts (p < .001). The receipt of chemotherapy at EOL was similar for both cohorts throughout the study period. Veterans who received care in regions with higher hospice admissions among Medicare beneficiaries were significantly less likely to receive AC at EOL (adjusted Odds Ratio (aOR): 0.13 95%CI: 0.08-0.23, P < .001) than veterans in regions with lower Medicare hospice use. Medicare HRR spending at the EOL was not associated with receipt of AC among Medicare beneficiaries (aOR): 1.004 95%CI: 1.00-1.009, P = 0.07). Conclusions: Perhaps due to availability of concurrent care, VHA patients received less aggressive care at EOL as compared to SM patients. At the regional level, greater hospice use among Medicare beneficiaries was significantly associated with reduced AC within the VHA.
Published: 2020

50. Genetic characterization of norovirus GII.4 variants circulating in Canada using a metagenomic technique

Author: Jennifer Ronholm, Nicholas Petronella, Sabah Bidawid, Oksana Mykytczuk, Jennifer Harlow, Nathalie Corneau, Menka Suresh, and Neda Nasheri
Subjects: 0301 basic medicine, Canada, Antigenic drift, Genotype, viruses, Biology, medicine.disease_cause, Genome, DNA sequencing, lcsh:Infectious and parasitic diseases, Astrovirus, Open Reading Frames, 03 medical and health sciences, medicine, Humans, lcsh:RC109-216, Amino Acid Sequence, Gene, Phylogeny, Caliciviridae Infections, Recombination, Genetic, Whole genome sequencing, Genetics, Sequence Analysis, RNA, Norovirus, High-Throughput Nucleotide Sequencing, virus diseases, biology.organism_classification, Recombination, Co-infection, 030104 developmental biology, Infectious Diseases, Metagenomics, Mutation, Next-generation sequencing, RNA, Viral, Capsid Proteins, Research Article
Abstract: Background Human norovirus is the leading cause of viral gastroenteritis globally, and the GII.4 has been the most predominant genotype for decades. This genotype has numerous variants that have caused repeated epidemics worldwide. However, the molecular evolutionary signatures among the GII.4 variants have not been elucidated throughout the viral genome. Method A metagenomic, next-generation sequencing method, based on Illumina RNA-Seq, was applied to determine norovirus sequences from clinical samples. Results Herein, the obtained deep-sequencing data was employed to analyze full-genomic sequences from GII.4 variants prevailing in Canada from 2012 to 2016. Phylogenetic analysis demonstrated that the majority of these sequences belong to New Orleans 2009 and Sydney 2012 strains, and a recombinant sequence was also identified. Genome-wide similarity analyses implied that while the capsid gene is highly diverse among the isolates, the viral protease and polymerase genes remain relatively conserved. Numerous amino acid substitutions were observed at each putative antigenic epitope of the VP1 protein, whereas few amino acid changes were identified in the polymerase protein. Co-infection with other enteric RNA viruses was investigated and the astrovirus genome was identified in one of the samples. Conclusions Overall this study demonstrated the application of whole genome sequencing as an important tool in molecular characterization of noroviruses. Electronic supplementary material The online version of this article (10.1186/s12879-018-3419-8) contains supplementary material, which is available to authorized users.
Published: 2018

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